The diagnosis of hairy cell leukemia (HCL) has traditionally been based on microscopic means. Immunophenotypic analysis of peripheral blood by flow cytometry is not widely recognized as a method for diagnosing HCL, perhaps due to the expectation of low yield of neoplastic cells in patients who are characteristically leukopenic. The abnormal coexpression of CD103, CD25, and intense CD11c and CD20 on monotypic, slightly large B-lymphocytes has previously been shown to be highly characteristic of HCL. We wished to determine if this pattern was valuable in the diagnosis of HCL in leukopenic patients with low levels of neoplastic cells in the peripheral blood. The abnormal immunophenotype above was observed in 25 peripheral blood specimens from patients with unexplained cytopenias or suspected lymphoproliferative processes. Ten of the 25 blood samples exhibited this abnormal phenotype in less than 5% of circulating leukocytes (ranging from