A patient with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) who was treated with alpha-interferon (alpha-IFN) is reported. After the treatment, the number of Ph+ bone marrow (BM) cells decreased gradually and the intensity of the rearranged major breakpoint cluster region (M-BCR) gene became faint; however, a lymphoblastic crisis developed about 1 year later. At the time of the blast crisis, the rearranged M-BCR band was detected, indicating that the blast crisis clone was derived from CML cells. The patient was treated with a combination of vincristine, prednisolone, daunorubicin, and L-asparaginase, and a hematologic remission was obtained. During the remission status, no rearranged M-BCR fragment was detected by conventional Southern analysis. Thus, the hematologic and genetic alteration in this case appeared to be identical to Ph+ acute leukemia with M-BCR rearrangement. The current case therefore indicates that alpha-IFN can reduce the proportion of Ph+ cells, but is unable to prevent blast crisis. Furthermore, the quantitative reduction of the cell population with a Ph chromosome may have some effects in modifying the genetic manifestations and clinical features of Ph+ CML, e.g., the delay in the appearance of the blast crisis.