Bone marrow biopsy specimens taken on initial investigation of 134 patients with hairy cell leukemia (HCL) were processed into plastic, and sections cut at 3 μm were used for histologic and histomorphometric evaluation. Twenty-four clinical, 10 histologic, and four histomorphometric variables were tested for their prognostic significance. Bone marrow involvement was found in all cases, and on the basis of their morphology, the hairy cells were divided into three types: ovoid (47%), convoluted (37%), and indented (16%); this classification proved to be highly significant in the test statistics, with median survivals for the three groups of 56, 12, and 5 months, respectively. The characteristic nuclear features of the three types also were identified in smears of peripheral blood, in sections of spleen, and by electron microscopy. In addition, significant differences were found when the patients were grouped according to the tumor cell mass (volume %) in the biopsy sections, with median survivals of 55, 21, and 8 months noted for <20 vol%, 20–50 vol%, and >50 vol%, respectively. Other factors with prognostic relevance were cytoplasmic inclusion bodies in the hairy cells (HC) and a number of clinical variables, including initial values of Hb and ESR, and platelets and monocytes in the peripheral blood. These results confirm that the bone marrow always is involved in HCL and its histology is diagnostic; that HCL may be classified according to the predominant neoplastic cell type; and that the patients may be staged on the basis of the tumor cell burden in the bone marrow biopsy.