In patients with diffuse large cell lymphoma (LCL), bone marrow involvement at the time of diagnosis is a poor prognostic sign. Since 1980, the authors have encountered 13 patients LCL who had simultaneous bone marrow involvement by small cleaved cell lymphoma (11 cases) or mixed small and LCL (two cases), a phenomenon known as "discordant" or "divergent" bone marrow histology. The patients ranged in age from 33 to 85 years (median, 61 years) and presented most commonly with Stage III or IV disease, independent of bone marrow involvement. Seventy-seven percent achieved complete remission (CR) with combination chemotherapy; 50% of these eventually relapsed and died of their disease. One patient died of unrelated causes. No recurrences of low-grade lymphoma were observed, as judged either by clinical behavior or rebiopsy. The survival of the patients with discordant bone marrow histology was compared with that of patients with LCL with or without bone marrow involvement by LCL. Of the 11 patients with discordant marrow histology followed for a minimum of 2 years, four (36%) are long-term survivors; this is comparable to the 2-year survival of patients with LCL without bone marrow involvement (45%). In contrast, 89% of patients with bone marrow biopsy specimens positive for LCL died within 18 months from the time of diagnosis (mean survival, 5.7 months). All diffuse LCL tested were of B-lineage. The authors attempted to determine whether the presence of discordant bone marrow histologic types indicated an underlying low-grade B-cell lymphoma in these patients by evaluating the peripheral blood of the long-term survivors for the presence of clonal excess. Of the three surviving evaluable patients tested, one had evidence of clonal excess in the peripheral blood. For patients with LCL who have a simultaneous bone marrow biopsy positive for low-grade lymphoma (discordant marrow histology), survival is no different from that of patients with negative marrows, and markedly better than that for patients with marrows positive for diffuse LCL. The biological significance of discordant bone marrow histology is not clear at this time.