A number of recurring chromosomal abnormalities have been identified in childhood acute lymphoblastic leukemia. Many of these correlate closely with clinical, morphologic, and immunophenotypic features present at diagnosis and are useful in predicting outcome. Furthermore, these abnormalities point the way toward understanding the biologic basis for this disease. Challenges for the future include improvement in the quality and rapidity of cytogenetic analysis, the use of molecular probes to detect specific chromosomal abnormalities accurately and efficiently, and the incorporation of cytogenetic information into planning therapy.