We studied cells from 30 controls and 85 cases of untreated B-chronic lymphocytic leukemia (CLL) with a fluorescence in-situ hybridization (FISH) technique utilizing a probe to chromosome 12. By use of a threshold of > 2% for trisomy 12 for the CLL cases (the mean +3 SD for controls was 1.3%), 20% (17/85) were trisomy 12. The mean % cells positive was 32.6 (median, 39.4; range, 2.4-79.1). There was a trend toward an higher incidence of trisomy 12 in patients with Rai stages 1-4 vs Rai 0 (p = 0.16). Forty-seven % (8/17) of patients with trisomy 12 had strong intensity CD20 antigen expression compared to 21% (14/68) of patients without trisomy 12 (p = 0.03). Trisomy 12 associated with CLL is easily detected by FISH with an overall incidence of 20%. This technique should be applied to larger groups of patients to confirm the potential variation among Rai stages and immunophenotypic subgroups.