Cytogenetic and molecular analyses are essential for the classification of childhood hematologic malignancies. Nearly all children with leukemia should have an adequate cytogenetic analysis which in 80-90% is expected to show clonal chromosomal abnormalities. Moreover, with the availability of appropriate gene probes and sophisticated molecular techniques, genetic rearrangements become detectable in the majority of leukemia patients. Genetic abnormalities often associate with particular clinical-biological characteristics of the disease. In ALL, for example, genetic alterations together with distinct immunologic and clinical features, define various subgroups. In AML, unique cytogenetic rearrangements have been identified and associated with distinct morphological subgroups. Apart from the diagnostic assessment, cytogenetic studies provide valuable prognostic information which may influence treatment choices. Molecular analysis has also become of important value in the management of children with leukemias, as it serves, for example, to identify genetic abnormalities not detected by chromosomal analysis and to monitor residual disease during treatment and follow-up. Thus, genetic analyses of leukemic cells provide information of clinical relevance as well as contributing to our understanding of leukemogenesis. Alternative classifications of acute leukemias which take into account genetic information are being proposed. The available cytogenetic and molecular data have then to be included in clinical protocols, either by selecting individualized therapies in certain leukemia subtypes or by modifying treatment according to quantification of residual disease. We are closer to our main goal which is not only to classify 100% of childhood leukemias accurately, but to cure all of them.