Cytogenetic analysis plays a pivotal role in the diagnosis and management of patients with hematologic malignancies. In research, the identification of specific chromosomal rearrangements associated with defined clinical groups has led to an explosion in the knowledge of basic mechanisms contributing to leukemogenesis. The strength of cytogenetic analysis is as a direct method for screening the whole genome. However, the interpretation of the banding pattern of highly rearranged chromosomes is often unreliable. Since the advent of molecular cytogenetic technologies based around fluorescence in situ hybridization (FISH), the accuracy of cytogenetic diagnosis has been considerably enhanced. Specific problems hampering the accurate analysis of leukemic karyotypes such as the low mitotic index, heterogeneity of the sample, and often poor morphology of chromosomes are also largely overcome by FISH. One of the most significant advances is the use of interphase FISH, which permits the use of nondividing cells as DNA targets and enables a large number of cells to be evaluated (1 –4 ). This has advantages for monitoring disease progression, response to treatment, and success of bone marrow transplantation. The simultaneous identification of cell type (by morphology or immunophenotype) and chromosome abnormality (by FISH) is also possible, allowing the identification of cell lineages involved in the neoplastic clone (5 ).