A case of Hodgkin's disease (HD) in a patient with long-standing hairy cell leukemia (HCL) is reported. The diagnosis of HCL was confirmed by clinical features (chronic illness with marked splenomegaly) and hematopathologic findings (increase of characteristic hairy cells with tartrate-resistant acid phosphatase activity in peripheral blood and bone marrow). Cervical lymphadenopathy first appeared 6 years after the diagnosis of HCL, and histologic features of the node were characteristic of HD. As it was possible that the neoplastic cells of both lesions might have originated from a single clone, their phenotypic features were defined. The hairy cells were found to bear surface immunoglobulin, receptors for complement components, leukocyte common antigen, and antigen defined by LN-1 monoclonal antibody, whereas lymph node lesion was characterized as HD because the Reed-Sternberg-like cells were positive for Leu M1 antigen, lysozyme, alpha-1-antitrypsin, and nonspecific cross-reacting antigen. Since there was no evidence indicating a common clonal origin, it is more likely to consider that both lesions are derived from different clones.