Polycythemia vera (PV) is a hematopoietic stem cell clonal disorder, 5 to approximately 10% of which will evolve into acute leukemia. The pathophysiology of leukemic transformation and the best therapy for the leukemic phase of PV is still unknown. A 73-year-old woman was given a diagnosis of PV 17 years previously. However, laboratory data revealed myeloblasts in the peripheral blood with macrocytic anemia and thrombocytosis in March 2003. Bone marrow examination in October 2003 revealed 32.8% myeloblasts with trilineage dysplasia. Chromosomal analysis of the bone marrow cells revealed that 18/22 of mitotic cells had del(20q) and 3/22 of had t(2; 12). The leukemic phase of PV was diagnosed. She achieved not only a hematologic remission, but also cytogenetic remission after interferon (IFN)-alpha treatment. As far as we know, this is the first report of the introduction of IFN-alpha in the treatement of the leukemic phase of PV. Further monitoring of this patient will provide valuable information concerning the pathophysiology of leukemic transformation and the development of effective therapy for the leukemic phase of PV.