A novel by Jeffrey Eugenides published in 2002 which went on to win the Pulitzer Prize for Fiction.

Calliope (later Cal) Stephanides was born with a rare genetic condition that caused him to look externally female, but in adolescence begin developing male characteristics.

Most of the book is a Generational Saga which recounts the story of Cal's parents and grandparents who happened to make such a trait possible.

If you want the English county region which very indirectly names this novel, Middlesex, England, is discussed under Home Counties, and its county cricket side gets a mention under Cricket

Middlesex contains examples of:

• A-Cup Angst: The absence of breast development during puberty was one of Calliope's big concerns while he still thought he was a girl.
• The Beard:
  • Jimmy Zizmo is this for Lina, who is a lesbian and had to leave Bithynios after her affair with another woman was discovered.
  • Callie has a brief fling with the Obscure Object's brother before Callie and the Obscure object consumate their relationship.
• Best Years of Your Life: Callie's carpool driver, Mrs. Drexel, tells this to the carpoolees. Callie, age 12, hates her for this.
• Blind Mistake: The fact that the doctor who delivered Callie was nearsighted and didn't notice his unusual genitalia had huge effects on the lives of everyone involved, especially Callie.
• Brother–Sister Incest: Siblings Desdemona and Lefty fell in love with each other, got married on the boat to America where nobody knew they were siblings, and had two children together. Because of the era they lived in, they knew that incest was taboo, but they had no knowledge of the genetic implications for their children until Desdemona was already pregnant.
• Closet Key: "The Obscure Object" for Cal, as meeting her gradually makes Cal realize his attraction to girls. As Cal was still living as female by this point, this was seen as deviant.
• Coitus Interruptus: The Object's brother stumbles upon a liaison between her and Callie. He subsequently blackmails Callie into breaking off their friendship.
• Didn't Think This Through: When Callie finds out that the doctor was lying to all of them about the presence of male gonads, their first reaction is to leave a "Dear John" Letter, take all the money they have, and cut their hair. It ends with them getting beaten up by two random thieves and arrested for taking part in an underground circus. Oh, and their father dies during a botched ransom attempt from the local priest. Tessie, when they reunite, has a lot of Anger Born of Worry.
• Earn Your Happy Ending: Despite all the tribulations of growing up intersex, Cal ends the novel finally getting into a romance with a woman named Julie who accepts him as he is.
• Elegant Classical Musician: Milton's clarinet skills are initially what make him attractive to Tessie. They even use it in foreplay.
• Faking the Dead: Jimmy Zizmo fakes his death and disappears after wrongly suspecting that the baby Lina gave birth to (Tessie) was not his; he turns out to have reinvented himself as Wallace Fard Muhammad and started the Nation of Islam.
• Framing Device: The modern-day segment of the story features Cal, now living as a man, working as a diplomatic attache in Berlin and trying to court a Japanese-American photographer named Julie Kikuchi who lives there.
• Generational Saga: Middlesex features multiple generations of the Greek-American Stephanides family as its protagonists. Desdemona and Lefty are of the first generation; Tessie and Milton are of the second generation; and our narrator Cal is of the third generation.
• Groin Attack: Played for drama. Certain forms of physical activity proved to be excruciatingly painful for Callie's undescended testes back before he was aware of them.
• Historical Domain Character: The book is historical fiction and features some famous real-life people:
  • General Hajienestis, the insane Greek commander in their war against Turkey.
  • Desdemona encounters Mustafa Kemal during the occupation of Smyrna.
  • Henry Ford, who watches Lefty perform in a pageant put on by the new factory workers.
  • Wallace Fard Muhammad, founder of the Nation of Islam, who in this novel is revealed to be the new identity that Jimmy Zizmo took on after faking his death.
• Hurt Foot Hop: When Calliope is running away from Jerome, he jumps over a historical marker, grazes it with his foot, and hops in pain.
• Important Haircut: One of the first things Calliope does to change to Cal is get a short haircut.
• Intersex Tribulations: Cal was raised female but began developing masculine characteristics upon hitting puberty due to 5-alpha reductase deficiency. Neither Cal nor his parents know about the underlying condition so Cal doesn't understand why he's not a "normal" girl. After the events involving the Obscure Object, Cal is taken to a sexologist named Peter Luce who finds out about Cal's unique genetics and anatomy. Luce has an agenda of wanting to prove his hypothesis that a person's gender identity can be completely molded by nurture regardless of that person's biology or innate desires, so instead of telling Cal about his intersex nature and giving him the choice of what to do with his own body, Luce keeps Cal in the dark while planning to send him for surgical removal of his male organs and progesterone therapy to force him to remain a girl. Upon discovering the truth Cal runs away and spends some time exploring before re-entering society as a boy.
• Justified Title: Middlesex refers not only to Cal's condition, but also to the street where he spent his late childhood and adolescence.
• Kissing Cousins: Tessie and Milton are a pair of second cousins who marry each other and have two children together, Cal and Chapter Eleven. They're second cousins because Tessie's mother Lina is a cousin of both of Milton's parents, the incestuous siblings Desdemona and Lefty.
• Large Ham: Cal's narration borders on this at times. Justified in that when it does, he's lampshading Greek epics, which have the tendency to do this.
• Last Het Romance: Julie Kikuchi tells Cal that she used to be dated by guys who were in denial about being gay; they wanted to see if they could be content settling for a woman with a boyish figure, but inevitably the guy would break up with Julie to date men instead. When Cal is initially afraid to get closer to Julie because he's afraid she won't accept his intersex body, Julie mistakenly fears he's another closeted gay man who was only using her to try and figure out his own sexuality. Then Cal works up the courage to come out to her as an intersex man and reassures her that she's the first woman with whom he wanted a serious relationship: in his words Julie is not a "last stop" for him, but rather a "first stop".
• Late Coming Out: Sourmelina (Lina for short) doesn't come out as a lesbian until she’s middle-aged, as her conservative family and the homophobic norms of both Greece and the USA in the early 20th century forced her to hide it.
• Mad Brass: The real-life Greek General Hajienestis features prominently in scenes set during the Greco-Turkish War; he's unable to command his troops effectively because he thinks that he's a corpse with legs made of glass.
• Married at Sea: On the passenger ship to America, Desdemona and Lefty take advantage of the fact that they're among strangers and their documents were conveniently lost in the sacking of their home, meaning there's no way for anyone to find out that they're siblings if they keep it a secret. Under the pretense of being strangers with no blood relation to each other, they put on a whole charade to be seen by their fellow passengers that progresses from Meet Cute to getting to know each other to a wedding on board the ship, all before they even arrive in America.
• Matchmaker Crush: Desdemona tries to get Lefty to marry one of the two eligible girls from their village, Lucille or Victoria. She helps get both of them dressed up, and sends Lefty off to meet them, but he is uninterested in either. After this she is forced to admit her feelings toward Lefty are not just sisterly.
• Maternity Crisis: One woman gives birth during the great fire of Smyrna, surrounded by fellow refugees crammed up against the harbor. She and her baby most likely died.
• Maternal Impression: After returning home from a vaguely sexualized production of the play The Minotaur, Desdemona and Lefty have sex, as do Lina and Zizmo. Desdemona, ashamed of her sexuality, pretends to be asleep. Milton and Tessie are both conceived that night, and the circumstances of their conception are not particularly imprinted on either of them. Years later, when those two children grow up, marry each other, and have Cal, he sees reflections of himself in his parents' conception.
  Cal: Parents are supposed to pass down physical traits to their children, but it's my belief that all sorts of other things get passed down, too: motifs, scenarios, even fates. Wouldn't I also sneak up on a girl pretending to be asleep? And wouldn't there also be a play involved, and somebody dying onstage?
• Merlin Sickness: Lefty develops a purely psychological version of this after his second stroke. Desdemona is terrified that he'll eventually regress past when they got together and think of her or refer to her as just his sister again.
• No Celebrities Were Harmed: The character Peter Luce is modeled on the controversial real-life sexologist John Money, who while not exactly a household name was still alive when this novel was published.
• No Periods, Period: Averted. Since Calliope does not have a uterus, he fakes having periods to avoid suspicion from his mother.
• One-Gender School: Cal goes to an all-girls' school, and it's noted that Pseudo Romantic Friendships are considered normal there.
• Only Known by Their Nickname: The Obscure Object (referencing the film That Obscure Object of Desire, since she's Cal's Closet Key), and Cal's brother Chapter Eleven (referencing how he eventually drives his father's company into bankruptcy).
• Pass Fail / Ambiguously Brown: It's somewhat complicated, but Jimmy Zizmo, Cal's maternal grandfather, invented the new persona of Wallace Fard Muhammad (a real person who founded the Nation of Islam) after faking his death. Additionally, the way his origins are discussed by the characters and the narration, Zizmo could genuinely be of mixed ancestry and passed as Greek, Turkish, and Polish before faking his death and assuming his new identity; or he could genuinely be Greek, Turkish, and Polish, and be passing as a mulatto. The novel is delightfully ambiguous about what he really is.
  Desdemona: An Arab? Is that why you didn't tell us about him in your letters?
  Lina: He's not an Arab. He's from the Black Sea.
  Desdemona: Pontian! He's not Muslim, is he?
  Lina: Not everybody from the Pontus converted. What do you think, a Greek takes a swim in the Black Sea and turns into a Muslim?
  Desdemona: But does he have Turkish blood? Is that why he's so dark?
  Lina: I don't know and I don't care.
• Pining After Protagonist's Parent: Cal's mother Tessie was originally engaged to Father Mike Antoniou, but she broke it off with him to marry her second cousin Milton instead. This is part of what motivates Mike to make fake ransom calls to Cal's parents after Cal runs away; Mike has spent so much time feeling inferior to Milton that he wants to get the better of him for once.
• Pizza Boy Special Delivery: To determine Callie's sexual orientation, Dr. Luce has him watch a low-budget porn film called "Annie Delivers To Your Door," in which the titular pizza girl has sex with a different man at each house, starting with a pool boy. Callie finds the film too raw and unpleasant-looking to be arousing, but he tells Dr. Luce that he's attracted to the pool boy because he knows that's what Dr. Luce wants to hear.
• Prenatal Gender Picking: After deciding they really want for their second child to be a daughter, Tessie and Milton indulge in a pseudoscientific theory to ensure that result: having sex right as Tessie ovulates, so that the "swifter" sperm bearing Y chromosomes will die before reaching the egg. It... doesn't actually work as intended.
• Prophecies Are Always Right: The first chapter describes Desdemona divining Tessie's unborn second child will be another boy through the use of a silver spoon, only for Callie to be born seemingly female. When Cal comes home identifying as a male, the aged Desdemona proudly declares her spoon wasn't wrong after all.
• Pronoun Trouble: Cal runs into a bit of this. According to Euginedes, this is why he wrote the novel in first person.
• Pseudo-Romantic Friendship: At Calliope's all-girls school this is stated to be considered normal, due to the belief that a certain amount of emotional energy which is normally reserved for crushes on boys gets redirected into friendships with other girls instead. However, Cal's friendship with the Obscure Object ends up becoming both romantic and sexual.
• Raised as the Opposite Gender: A non-standard case. Tessie and Milton did specifically want their second child to be a daughter, but they didn't raise Cal as a girl despite knowing he was born male; rather they and the doctors missed the signs of Cal being intersex and raised Cal in the mistaken belief they were dealing with a cisgender, endosex^note meaning non-intersex, also known as perisex or dyadic daughter.
• Rock–Paper–Scissors: Lefty and Desdemona play Rock-Ax-Snake (Ax breaks Rock, Snake swallows Ax, Rock kills Snake) when she's trying to persuade him to marry one of the two eligible girls in Bithynios. Lefty wins both rounds, so he doesn't have to marry either of them.
• The Runaway: Calliope becomes one after realizing that Peter Luce is lying to him and wants to remove his male organs. He cuts his hair, remakes himself as Cal and ends up in San Francisco as part of a strip club show as "Hermaphroditus", where he meets an intersex woman named Zora Khyber who serves as a mentor.
• Secret-Keeper: Lina does not tell anyone her cousins Desdemona and Lefty are siblings, and in exchange they don't tell anyone that Lina is a lesbian.
• Shown Their Work: The amount of research the author did on the history of Greece, the history of Detroit, and Cal's biological condition really shows.
• The Speechless: Lefty loses the ability to speak after his first stroke and adapts by writing on a chalkboard.
• Sperm as People: Inverted; Cal imagines himself and Chapter Eleven as tiny homunculi inside their eggs, waiting to be fertilized.
• Tangled Family Tree: Cal's family tree looks like this due to all the incest; her grandparents were a pair of siblings, and her parents were a pair of second cousins.
• Traumatic Haircut: In the concessions area at Ellis Island, Desdemona went into a YWCA that gave her a makeover, including giving her a '20s Bob Haircut and a cloche hat. Desdemona is angered and humiliated by this, and vows never to cut her hair again.
  Desdemona: That's the last time anyone cuts my hair.
  Lefty: You look fine. You look like an Amerikanidha.
  Desdemona: I don't want to look like an Amerikanidha. That's the last haircut.
• What Happened to the Mouse?: In story, Cal comments that people are probably wondering what happened to Desdemona since she seemingly drops out of the story. Turns out that she's still alive and has just retreated to her room, and lives long enough to see Cal's new male persona and confess the reason he's the way he is.
• While Rome Burns: A British naval vessel refuses to rescue Greeks from Smyrna, nonchalantly watching the city burn and refugees drown. They're even playing orchestral music as Desdemona and Lefty sail past on another ship.
• Wrong Genetic Sex:
  • As the result of 5-alpha-reductase deficiency. Genetically, Callie is 46,XY, but lacks the enzyme that converts testosterone to its active form. Thus, he has cryptorchid (undescended) testes, no ovarian or uterine structures, a nonfunctional vaginal pouch, and a microphallus (such that it's repeatedly mistaken for a larger-than-normal clitoris, both by Cal and by several doctors).
  • Also applies to Zora Khyber, a performer in Bob Presto's burlesque club who is affected by complete androgen insensitivity syndrome and who—although being able to pass as a female—identifies as intersex due to her XY chromosomes.
• Wrong-Name Outburst: In his youth, Lefty visited a brothel and chose a girl who resembled the sister he truly wanted. He called the prostitute by Desdemona's name. (He was high at the time.)
  Irini: By the way, I'm Irini. We don't have a Desdemona here.