The blast phase of chronic myelogenous leukemia (CML) frequently is associated with cytogenetic evidence of clonal evolution, defined as chromosomal aberrations in addition to the t(9;22)(q34;q11.2). We identified the t(8;21)(q22;q22) and other cytogenetic abnormalities by conventional cytogenetics and fluorescence in situ hybridization in 2 patients with t(9;22)-positive CML at the time of blast phase. The t(8;21), which typically is associated with a distinct subtype of de novo acute myeloid leukemia (AML) carrying the aml1/eto fusion gene, was accompanied by increased bone marrow myeloblasts (33%) in case 1 and extramedullary myeloid sarcoma in case 2, suggesting its possible role in disease progression. In case 1, the leukemic cells in aspirate smears had salmon-colored cytoplasmic granules, and immunophenotypic studies showed that the blasts expressed CD19. These findings suggest that the pathologic features of blast phase CML with the t(8;21) resemble those of de novo AML with the t(8;21).