Anecdotal literature reports and the authors' own observations suggest an association between chromosome 8 aneuploidy and leukemia cutis. The authors investigated this potential association by using fluorescence in situ hybridization (FISH) directly on skin infiltrates in a series of 11 patients with acute monocytic leukemia (AML). Seven of the 11 patients were aneuploid for chromosome 8 by FISH which was confirmed by dual color hybridization. Six of these seven patients were AML-M4 or M5 and one was M1. The majority of the cases with leukemia cutis expressed CD4 (90% of cases), CD14 (60%), and/or CD56 (50%) in bone marrow leukemic cells. The data show the utility of examination of skin infiltrates by FISH for the detection of trisomy 8 in leukemia cutis. They also suggest the importance of trisomy 8 as a factor in predisposition to skin infiltration in AML.