The t(8;21)(q22;q22) rearrangement is observed in about 15% of acute myelocitic leukemia (AML) cases, while variant t(8;21) translocations are detected in 6-10% of AML patients positive for the 5'RUNX1/3'CBFA2T1 fusion gene. We report a detailed molecular cytogenetic analysis of a four-way variant t(8;11;16;21)(q22;q14;q12;q22) performed by fluorescence in situ hybridization with specific BAC and PAC clones. The study demonstrated the loss of several megabases belonging to chromosomes 11 and 16 whereas no deletion was detected on der(21). These findings suggest that a precise breakpoint characterization could identify submicroscopic genomic deletions whose meaning remains to be defined.