We analyzed prevalence, characteristics, clinical correlates, and prognostic significance of autoimmune cytopenia in patients with chronic lymphocytic leukemia. Seventy of 960 unselected patients (7%) had autoimmune cytopenia, of whom 19 were detected at diagnosis, 3 before diagnosis, and 48 during the course of the disease. Forty-nine patients had autoimmune hemolytic anemia, 20 had immune thrombocytopenic purpura, and 1 had both conditions. A clear association was observed between autoimmune cytopenia and poor prognostic variables (ie, high blood lymphocyte count, rapid blood lymphocyte doubling time, increased serum β-2 microglobulin level, and high expression of ζ-associated protein 70 and CD38). Nevertheless, the outcome of patients with autoimmune cytopenia as a whole was not significantly different from that of patients without this complication. Furthermore, no differences were observed according to time at which cytopenia was detected (ie, at diagnosis, during course of disease). Importantly, patients with advanced (Binet stage C) disease because of an autoimmune mechanism had a significantly better survival than patients in advanced stage related to a massive bone marrow infiltration (median survivals: 7.4 years vs 3.7 years; P = .02). These results emphasize the importance of determining the origin of cytopenia in patients with chronic lymphocytic leukemia for both treatment and prognostic purposes.