The translocation (8;21) is a typical marker of the M2 subtype of acute nonlymphocytic leukemia, whereas the Philadelphia (Ph) chromosome is predominantly associated with chronic myelogenous leukemia, and seldom with immature acute leukemias, either lymphoblastic or nonlymphoblastic. Furthermore, the association between t(8;21) and a Ph in the same cell is extremely rare. We present a case of secondary acute promyelocytic leukemia with a karyotype 46,XY,t(8;21), t(9;22) at onset. At relapse the patient lost the Ph, while maintaining the t(8;21). This apparently paradoxical pattern of cytogenetic features and evolution is discussed.