Fluorescence in situ hybridization (FISH) is a powerful tool for the analysis of chromosomal abnormalities in metaphase and interphase cells. Interphase cytogenetics has become an important technique for the analysis of leukemias, since in many cases it may be difficult to obtain metaphase spreads representative for the malignant clone(s). Using suitable DNA probes, leukemia samples can be screened for the most relevant chromosomal abnormalities. Alternatively, chromosomal imbalances can be identified by applying the new approach of comparative genomic hybridization. In this review, recent advances in the analysis of leukemia made possible by FISH are presented and future prospects of molecular cytogenetics are discussed.