Virtually all cases of childhood acute lymphoblastic leukemia have chromosomal abnormalities. Non-random chromosomal abnormalities have been correlated with leukemic cell lineage, the degree of cell differentiation and certain clinical and biologic features. Cytogenetic findings have prognostic significance, but the adverse influence of many rearrangements, including most chromosomal translocations, may be offset by the greater cytoreductive effects of intensified therapy. Cytogenetic abnormalities have also provided focus for molecular studies of leukemogenesis. Such studies have recently identified key genes and their protein products which play important roles in malignant transformation and proliferation.