Mantle cell lymphoma (MCL) patients represent a difficult problem, sometimes to establish the diagnosis but mostly because of their refractoriness to standard lymphoma treatments. Which treatments to apply and to whom is not yet defined. In this study, we attempted to analyze the clinical features, to identify the major prognostic factors, and to evaluate the outcome of 121 MCL patients treated in our institution between 1979 and 1997. Clinical data, treatment modalities, and International Prognostic Index (IPI) score were evaluated. Median age was 63 years. Patients usually presented with advanced stage disease (87%), disseminated lymph nodes (57%), bone marrow involvement (79%), but with a good performance status (PS) (81%). Lymphocytosis >4000/microl and/or peripheral blood involvement was present in 36% of cases, and gastrointestinal disease in 18%. The t(11;14)(q13;q32) and/or bcl-1 rearrangement was detected in 47/57 studied cases. Median overall survival (OS) was 3.12 years and a longer survival was significantly associated with younger age (<70 years), good PS (<2), localized disease (stage I-II), fewer than two extra-nodal sites, absence of spleen or peripheral blood involvement, normal serum LDH and beta2-microglobulin levels, and hemoglobin level greater than 12 g/dl. However, the IPI failed to identify patients with longer OS and in a multiparametric analysis, only older age, hemoglobin less than 12 g/dl, poor PS, and blood involvement were associated with a poorer outcome. Treatment modalities had no impact on survival with 75% of patients relapsing or progressing. Our data showed that the poor outcome of MCL patients is mainly related to adverse patient characteristics, a highly disseminated tumor, and some unknown parameters associated with the refractoriness to standard therapy.