We report a case of hairy cell leukemia variant developing in a background of polycythemia vera in a 77-year-old man who presented with lymphocytosis and splenomegaly. Classic hairy cell leukemia in a patient with polycythemia vera has been reported previously, but hairy cell leukemia variant arising in a patient with polycythemia vera has never been described to the best of our knowledge. Initial testing of the peripheral blood showed circulating medium to large leukemic cells with large, centrally placed nuclei, each containing a prominent nucleolus, and some cells showed cytoplasmic projections. A bone marrow biopsy had marked myeloid and erythroid hyperplasia and interstitially distributed cells with a fried-egg appearance. We verified a monoclonal B-cell population by flow cytometric analysis, which revealed expression of bright CD11c, CD22, and CD103 expression, and a lack of CD25 expression. The patient received a 5-day course of cladribine and subsequently had a complete remission. Approximately 2 months later, he had a relapse and was treated with pentostatin; however, he had no clinical response and died.