OBJECTIVE To evaluate whether there is an association between the presence of t(14;18) and bcl-2 gene expression, on one hand, and clinical presentation and outcome, on the other hand, in patients with follicular small cleaved cell lymphoma (FSCCL) and diffuse large cell lymphoma (DLCL), in light of conflicting reports concerning the prognostic significance of these parameters. METHODS Retrospective cohort study and molecular analysis of archived tissue. METHODS Tertiary care hospital. METHODS Sixty-two patients with non-Hodgkin's lymphoma, of whom 33 (13 women and 20 men) had FSCCL and 29 (9 women and 20 men) had DLCL. Their ages ranged from 27 to 88 years. METHODS Presence of t(14;18) was determined using Southern blot analysis or polymerase chain reaction or both. The level of bcl-2 gene expression was determined by immunohistological analysis using a monoclonal mouse anti-human antibody (DAKO-Bcl-2, 124). METHODS Clinical stage of lymphoma at diagnosis and responsiveness to treatment, and the correlation between these clinical parameters and t(14;18) status and bcl-2 gene expression. RESULTS There was no clear association between t(14;18) status and prognosis for either FSCCL or DLCL. In contrast, high bcl-2 expression clearly predicted a generally poor prognosis in patients with FSCLL (p = 0.0146) and indicated resistance to treatment in those with DLCL (p = 0.0853). CONCLUSIONS In non-Hodgkin's lymphoma, level of bcl-2 gene expression may represent a useful, independent prognostic indicator to identify high-risk patients and choose specific therapeutic approaches.