Splenic lymphoma with villous lymphocytes (SLVL) represents a low-grade B-cell non-Hodgkin's lymphoma (NHL) that histologically is indistinguishable from splenic marginal-zone lymphoma (SMZL). Characteristic features of SLVL are splenomegaly, moderate lymphocytosis, nodular and intrasinusoidal pattern of bone marrow infiltration, serum monoclonal band, slow benign course, and response to splenectomy. The diagnosis is made by the morphology of the circulating villous cells and their immunophenotype, which is distinct from that of chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), diseases with which SLVL may be confused. When treatment is indicated, splenectomy is the treatment of choice, but some patients may require additional chemotherapy to control progression. In those circumstances, fludarabine may be the agent of choice. Despite its unique features, which, compounded, suggest that SLVL is a clinicopathologic entity, there are no specific chromosome abnormalities and problems of differential diagnosis with other B-cell NHLs, chiefly mantle-cell lymphoma (MCL), remain in a minority of patients.