The molecular mechanisms responsible for progression of chronic myelogenous leukemia (CML) to blast crisis have not been well defined. Blast crisis may be partially related to inactivation of tumor suppressor genes/such as p53 or retinoblastoma (Rb) gene. There is evidence for an association of blast cell phenotypes in CML with alterations of these genes: a strong association of myeloid phenotypes with abnormalities of the p53 gene and a weaker association of lymphoid phenotypes with abnormalities of the Rb system. We found a marked decrease in Rb gene product and rearrangements of the p53 gene simultaneously in two cases of biphenotypic blast crisis of CML (myeloid and B-lymphoid). These results support the association of blast cell phenotypes with alterations in tumor suppressor genes in CML blast crisis.