Fluorescence in situ hybridization (FISH) is becoming popular in the diagnosis of clonal chromosomal abnormalities. We set up a fast FISH procedure using an extensive set of specific probes. Conventional banding analysis (CBA) and FISH were compared in 260 newly diagnosed acute myeloid leukemia (AML) patients. For FISH the following probes were used: MLL, CBF-beta/MYH11, ETV-6/AML1; AML1/ETO, BCR/ABL, PML/RAR, c-MYC, TP53, RB1, 5q31/5p15.2, 5q33-34, 7q31/CEP7, 20q13; CEP 4, X, Y. Result time was 96 h for CBA versus 5 h for FISH from direct harvest. CBA showed clonal abnormalities in 41% (n=105/260), normal karyotype in 39% (n=102/260) and failed in 20% (n=53/260). FISH screened all patients and detected abnormalities in 39% (n=102/260); CBA and FISH together identified abnormalities in 49% (n=128/260). In six patients with normal CBA and in eight patients with clonal karyotype, it detected further cryptic abnormalities. CBA showed clonal abnormalities in 13% of patients negative at FISH (n=21/158). FISH screening does not add relevant information to CBA, but is the quickest method for detecting major genetic abnormalities in AML. The speed of FISH is very valuable in AML-M3/M3v because PML/RAR+ patients require specific therapy. Furthermore, we suggest FISH screening in failed, complex or suboptimal quality chromosome and specific FISH analysis for 5q, 7q, 12p, 17p, inv(16), t(11q23) in order to implement CBA accuracy.