The goal of this study was to analyze the presenting features, natural history, and prognostic factors in 59 patients with well characterized mantle cell lymphoma (MCL). Cases were classified as nodular or diffuse and as typical or blastic variants. Age, performance status (PS), histologic variants, mitotic index (MI), hematologic parameters, tumor extension data, and International Prognostic Index (IPI) were recorded and evaluated for prognosis. The median age of the patients was 63 years (range, 39-83 years), and the male to female ratio was 3:1. Fifty-three patients had typical histology (3 nodular and 50 diffuse), and 6 had the blastic variant. Approximately 95% of patients presented with advanced stage disease (Ann Arbor Stage III-IV). Leukemic expression was observed in 58%. Complete and partial response rates were 19% and 46%, respectively. Parameters associated with lower response rate were Stage IV, high/intermediate or high risk IPI, and increased lactate dehydrogenase (LDH) level. In the logistic regression analysis, high LDH level and Stage IV disease were associated independently with lower response rate. Median survival was 49 months. Parameters associated with a short survival were: poor PS, splenomegaly, B-symptoms, MI > 2.5, leukocyte count > 10 x 10(9)/L, high LDH level, blastic variant, and high/intermediate or high risk IPI. In the Cox proportional hazards regression model, only poor PS (relative risk RR = 3.3; P = 0.002), splenomegaly (RR = 2.8; P = 0.007), and MI > 2.5 (RR = 2.4; P = 0.012) were associated with short survival. In this series, patients with MCL presented with advanced stage and extranodal involvement. Only a minority of patients achieved a complete response. The median survival was 4 years, with PS, splenomegaly, and MI being the most important factors predicting survival. These results show clearly that more effective therapies for MCL are needed.