Twenty-six patients with hairy cell leukemia have been evaluated clinically at Stanford University Medical Center and the M. D. Anderson Hospital and Tumor Institute since 1973. Only four patients had obvious leukemia and readily identifiable hairy cells in the peripheral blood. The remaining patients were pancytopenic, and hairy cells in peripheral blood were difficult to recognize. In 20 of the latter patients the marrow aspirates were unsuccessful or nondiagnostic. Bone-marrow biopsy was the primary method of diagnosis in 18 cases and proved the most reliable and pertinent diagnostic procedure in identifying this disorder. A well-defined water-clear rim of cytoplasm surrounding and separating the hairy cell nuclei was the main histologic feature, in contrast to the lack of visible cytoplasm and close appositon of lymphocytes in chronic lymphocytic leukemia or poorly differentiated lymphocytic lymphoma. The uniformity and blandness of the nuclei distinguished hairy cells in tissue sections from the cells of histiocytic lymphoma and acute myeloid leukemia. Awareness of the importance of the histologic appearance of the bone-marrow biopsy in hairy cell leukemia is essential in establishing an accurate diagnosis.