Fifty-eight patients with immunoblastic lymphoma (IBL) were the object of this study. Fifteen of them (26%) developed IBL during or after other diseases, either immunologic or neoplastic, including angio-immunoblastic lymphadenopathy, autoimmune disorders, chronic lymphocytic leukemia, Waldenström's disease, lymphoplasmacytoid lymphoma and Hodgkin's disease (subsequent IBL). The comparison between de novo and subsequent IBL revealed a significantly higher incidence of bone marrow involvement and bulky abdominal disease in the latter group, with a lower response rate to chemotherapy. The favorable primary extranodal disease of Waldeyer's ring exclusively belonged to de novo IBL, whereas the frequency of immunoglobulin abnormalities was higher in the subsequent IBL group (67%). The stage of disease, systemic symptoms at diagnosis and response to therapy were predictive of survival. The overall complete remission (CR) rate in the whole series was 37% and the median overall survival 14 months. Complete remitters have a median survival in excess of 60 months; all relapses occurred within the first 12 months of CR. No CNS relapse terminated the CR, and CNS prophylaxis seems unnecessary in IBL. The analysis of subsequent IBL may provide information on the pathogenesis of non-Hodgkin's lymphomas; the still poor prognosis of IBL deserves new therapeutic attempts to improve on the standard regimens.