Cytogenetic data have significantly contributed to our understanding of the heterogeneity of acute myeloid leukemia (AML). In AML, numerous recurrent chromosomal aberrations have been identified, and several of them, e.g. t(8;21)(q22;q22), t(15;17)(q22;q11-12), inv(16)(p13q22), are specific for distinct subgroups. Furthermore, chromosomal aberrations have proved to be of paramount prognostic importance for remission induction and survival. Chromosome analysis using classical cytogenetic banding techniques often fails to completely resolve complex karyotypes and cryptic translocations not identifiable by these techniques have been detected using molecular cytogenetic methods. While fluorescence in situ hybridization (FISH) has become an indispensable tool for screening and follow-up of known aberrations, the techniques of spectral karyotyping (SKY) and multiplex-fluorescence in situ hybridization (M-FISH) allow for the simultaneous visualization of all chromosomes of a metaphase in a single hybridization step, and thereby enable screening for the aberrations present without their prior knowledge. Therefore, with the introduction of these techniques in 1996 the comprehensive analysis of complex karyotypes and the identification of new, hitherto cryptic translocations and, ultimately, the identification of new disease subgroups seemed possible. Since, more than 600 cases of AML and MDS have been analyzed. Herein, we attempt to summarize the data published and discuss what has been achieved towards realization of these goals.