Context: The diagnosis of nodular lymphocyte predominant Hodgkin lymphoma involves key histopathologic and immunophenotypic findings. Appropriate classification is essential owing to the unique therapeutic and prognostic implications of this diagnosis.

Objective: To define the histologic and immunophenotypic features useful in diagnosing nodular lymphocyte predominant Hodgkin lymphoma and to identify the important differential diagnostic considerations. Diagnostic difficulty can arise in differentiating nodular lymphocyte predominant Hodgkin lymphoma from classical Hodgkin lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, follicular lymphoma (floral variant), and follicular hyperplasia with progressive transformation of germinal centers.

Design: Discussion of illustrative cases including morphologic and immunophenotypic findings.

Results: With the morphologic and immunophenotypic methods described, a diagnosis of nodular lymphocyte predominant Hodgkin lymphoma can be made on excisional biopsies.

Conclusion: Clinical, histologic, and immunophenotypic features are invaluable in reaching an accurate diagnosis.