We describe the application of fluorescence in situ hybridization (FISH) in a case of suspected chronic myelogenous leukemia (CML), cytogenetically characterized by a t(21;22) with no clear involvement of chromosome 9. The dual color FISH technique, performed using specific painting probes for chromosomes 9,21,22 and a BCR/ABL translocation probe, enabled us to confirm the diagnosis of CML by detecting the BCR/ABL rearrangement on chromosome 22q and the involvement of chromosome 9 in a variant translocation t(9;21;22).