Comparative genomic hybridization (CGH) and multiplex-fluorescence in situ hybridization (M-FISH) were used to evaluate the presentation karyotype in 15 and 18 patients respectively, aged >/=60 years, with acute myeloid leukemia (AML). Conventional G-banded analysis was performed in all patients prior to evaluation. Comparative genomic hybridization confirmed the G-banded karyotype fully in 12 patients and partially in two patients. Normal CGH profiles were observed in patients with a normal karyotype and in one patient with a balanced chromosomal translocation as the sole cytogenetic aberration. Multiplex-fluorescence in situ hybridization provided additional information in two patients with a complex karyotype, but failed to detect a telomeric translocation in one patient. Eight patients with normal G-banded karyotypes appeared normal by M-FISH. These results demonstrate that both CGH and M-FISH analysis correlate well with the G-banded karyotype in AML. Furthermore, although additive cytogenetic data was not provided by either technique in cases with normal karyotype, DNA copy number change and cryptic translocations below the resolution of CGH and M-FISH may still be the initiating event for leukemogenesis for these patients.