Among 172 patients with hairy cell leukemia (HCL) seen at the University of Chicago over a 10-year period, 15 were found to have a second malignancy. Neoplasia of the skin was noted most frequently; there were three cases of basal cell carcinoma, one case of anaplastic squamous cell carcinoma, and one case of malignant melanoma. This was followed in frequency by three cases of carcinoma of the lung. The clinical characteristics of these 15 patients did not differ from those of the general population of patients with HCL. A variety of second hematologic malignant disorders and solid tumors were identified. In one case, the second neoplasm occurred before the diagnosis of HCL; six were diagnosed concurrently; and eight followed the diagnosis of HCL. Since HCL is a well-defined clinicopathologic entity, patients with HCL who exhibit unusual features of the disease should be investigated further for the presence of second malignancies.