A patient with the M2 subtype of AML who had a 45,X,-X,t(8;21) karyotype at diagnosis was found to have the Ph chromosome in one out of 37 evaluated cells 18 months after the initial diagnosis. Interphase FISH studies utilizing a BCR-ABL dual-color probe did not detect a fusion product 4 months prior to the appearance of one Ph-positive cell. Nineteen months post diagnosis and 5 months after clinical relapse all evaluated cells had the Ph chromosome in a clone characterized by t(8;21). These observations suggest that late appearing Ph is a secondary event which may be either therapy-related or consistent with one of the later events in a multistep pathogenesis of AML.