The del(15q) chromosomal abnormality is known to occur in acute leukemias, but has rarely been described in chronic myelogenous leukemia (CML). Described here are five cases of CML associated with del(15q): four men and one woman. Bone marrow aspirate smears showed increased blasts in all cases at the time of del(15q) detection, in accelerated phase in two cases and myeloid blast phase in three. Conventional cytogenetic analysis showed t(9;22) and del(15q), as well as other inconsistent clonal abnormalities. All patients received imatinib mesylate; four received additional chemotherapy, and two had allogeneic stem cell transplantation (ASCT). Of the three patients who did not receive ASCT, one died, one was in persistent blast phase, and one was in clinical remission with molecular evidence of residual disease at 16, 6, and 34 months, respectively, after identification of the del(15q). Of the two patients who had ASCT, one died and one was in clinical remission with molecular evidence of disease at 15 and 64 months, respectively, after identification of the del(15q). These findings indicate that del(15q) is a recurrent cytogenetic abnormality that may be seen at initial presentation of advanced disease or may emerge during disease progression. Del(15q) appears to be associated with a poor prognosis in CML.