The overall survival of patients with hairy cell leukemia (HCL) has significantly increased in recent years because of the development of effective treatments such as interferon alpha and purine analogs. Several reports have described an increased risk of secondary cancers, particularly solid tumors, in patients with HCL. We describe a case of a patient with HCL, who had prolonged pancytopenia after a single course of cladribine. Fifteen months after the diagnosis of HCL the patient developed acute myeloid leukemia (AML) and died shortly afterwards. Review of the literature shows few reports of acute leukemia in HCL patients. All of the 11 reported cases of leukemia in patients with HCL have been in patients who have been treated with either interferon alpha or purine analogs, and developed several years (mean 4.3 years; range 1.6-6.4 years) after the diagnosis of HCL. Our case is unusual in that the patient developed AML shortly (1.2 years) after the diagnosis and treatment of HCL. Further studies are needed to clarify whether leukemias seen in patients following the treatment of their HCL are incidental findings or related to HCL and its treatments.