Analysis of chromosomal abnormalities present in the malignant cells of patients with leukemia has provided much information of diagnostic and prognostic importance. The cloning of genes rearranged by translocation breakpoints has provided insights into both the regulation of normal cell growth and differentiation and the pathogenesis of human malignancies. This article reviews recent analyses of the association of specific karyotypic changes with other disease characteristics, including treatment outcome. Also covered is the substantial progress that has been made in the molecular analysis of genetic abnormalities in leukemia, with emphasis on those changes produced by chromosomal rearrangements. The use of information derived from these latter studies to develop polymerase chain reaction and fluorescent in situ hybridization assays for clinical use is also summarized.