The t (9;22) translocation is present in about 95 per cent of chronic myelogenous leukemia and in a significant subset of acute leukemias, mainly of the lymphoid subtype. This chromosomal rearrangement leads to the fusion of the bcr and c-abl genes and to the transcription of leukemia-specific bcr-abl mRNAs. The accurate identification of the t (9;22) translocation relies on cytogenetics (conventional or Fish) and molecular techniques. The detection of residual Ph positive cells following bone marrow transplant or interferon therapy is critical and has relevant therapeutic implications.