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We report a patient with B-cell prolymphocytic leukemia (PLL) who was treated successfully with the monoclonal anti-CD20 antibody (rituximab). The patient had recurrent infections due to relative neutropenia, secondary to bone marrow infiltration. After treatment with monoclonal anti-CD20 antibodies (rituximab) 375 mg/m2 weekly for 4 weeks, complete remission was obtained. It was documented by normalization of peripheral blood counts, disappearance of organomegaly, and by molecular cytogenetics-fluorescent in situ hybridization (FISH) on bone marrow cells. She remains in complete remission 8 months following the discontinuation of treatment. This is the second reported case of successful treatment of B-cell PLL with rituximab.