Immunohistochemical and immunophenotypic analyses were performed on 278 cases of karyotypically abnormal non-Hodgkin's lymphoma (NHL). Excluding cases of lymphoblastic lymphoma or mycosis fungoides, 20 cases showed evidence of non-B cell lineage. T cell lineage was proven by genotypic and immunophenotypic analyses in 15 of the 20 cases; five were of ambiguous lineage. All of the non-B lineage cases were of diffuse histology with a large cell component (DLCL). Twelve cases expressed the Ki-1 antigen; five of these cases also demonstrated a translocation with a break at 5q35. Patients with Ki-1 positive DLCL and t(5q35) had a younger median age compared with non-B cell DLCL without t(5q35). The Ki-1 positive patients had a higher frequency of skin involvement and lower incidence of bone marrow involvement compared with Ki-1 negative DLCL. Survival analysis was performed on 86 cases of B cell DLCL and 18 cases of non-B cell DLCL which were serially ascertained prior to receiving cytotoxic chemotherapy. Median duration of complete remission was significantly longer in the B cell compared with the non-B cell DLCL groups; there was only a trend for decreased overall survival in the non-B cell group. Among the subset of non-B cell lymphomas, overall survival of patients with Ki-1 expressing DLCL was significantly longer than those with Ki-1 negative DLCL, who had a median survival of less than a year. These results show that immunophenotypic, immunohistochemical, and cytogenetic markers can define subsets of patients with non-B cell lymphomas with differing clinical characteristics and outcome.