We have studied 19 cases of splenic marginal zone B-cell lymphoma (SMZBCL) combining cytological features, conventional cytogenetics, and in situ hybridization (ISH) techniques. A clonal chromosome abnormality was found in 11/19 patients (58%). The more frequent recurrent abnormalities were: del(3), del (7q), and involvement of chromosomes 1, 3, 7 and 8. No patient showed the translocation t(11;14)(q13;q32). An outstanding finding was the low incidence of trisomy 3 (36%) compared to patients with MALT lymphoma. These findings support the interpretation that SMZBCL is a distinct lymphoproliferative disorder.