A clinicopathologic analysis of 35 cases of lymphocyte predominance Hodgkin's disease (LPHD) was performed, and the relationship between various histologic features and stage at presentation was examined. The series comprised 31 male and 4 female patients with a median age of 32 years. Twenty patients had Ann Arbor Stage I disease; 5, Stage II; 8, Stage III; and 2, Stage IV. Eight cases showed a multifocal epithelioid histiocytic reaction; six of these had advanced-stage (III or IV) disease (P = 0.003). Five cases contained relatively frequent atypical mononuclear cells; four of these were Stage III or IV (P = 0.017). A purely diffuse growth pattern was also associated with high stage (P = 0.031). Presence of nodularity correlated with low stage (P = 0.031). During follow-up (median, 4 years; range, 2.5 months-18 years) there was a high incidence of second neoplasms (2 large cell lymphomas, 3 non-hematologic malignancies). LPHD manifests greater diversity of stage at presentation than originally thought. A high content of epithelioid histiocytes, relatively frequent atypical mononuclear cells, and diffuse histology appear to define subsets associated with advanced-stage disease. The correlation of nodular growth pattern with low-stage disease is consistent with the distinctive behavior and derivation of nodular LPHD.