Two subtypes of splenic marginal zone lymphoma (SMZL) are identified in the World Health Organization (WHO) classification: SMZL without villous lymphocytes and SMZL with villous lymphocytes in the peripheral blood (SLVL). SLVL is a rare leukemic and indolent B-cell chronic lymphoproliferative disorder (B-CLPD) that we have to differentiate from hairy cell leukemia (HCL), B prolymphocytic leukemia (B-PLL) and follicular lymphoma (FL). Morphological examination associated with immunophenotyping is, in most cases, likely to distinguish these CD5 negative entities. However, the diagnosis can be difficult to make on morphological criteria, especially in patients without absolute lymphocytosis. Based on histologic, cytogenetic and molecular studies, SLVL emerges as a distinct entity. SLVL has a relatively clinical benign course but a few patients could require treatment, because of a symptomatic splenomegaly and/or a severe cytopenia. In symptomatic patients HCV negative, the frontline treatment remains questionable. Splenectomy, regarded as the most effective treatment, could be required for diagnostic purposes: however, relapse occur in 30% of cases. Fludarabine (FDR), a purine analogue and deoxycoformycin (DCF) can induce a maintained response in a substantial proportion of patients with SLVL and could be used as a first line treatment. In HCV + SLVL patients, antiviral treatment using alpha interferon and ribavirin can induce regression of SLVL.