Conventional cytogenetic studies have suggested that trisomy 12 may be a characteristic nonrandom numerical chromosome anomaly in benign ovarian tumors, particularly sex cord-stromal tumors. To confirm this finding, and to avoid possible culture artifact introduced during cytogenetic analysis, the authors performed fluorescence in situ hybridization (FISH) in paraffin-embedded samples of select ovarian neoplasms. Forty-four ovarian fibromas and granulosa cell tumors and 31 benign and borderline epithelial ovarian tumors were examined for the presence of trisomy 12. Trisomy 12 was detected in 40% (8 of 20) of the fibromas. No evidence of trisomy 12 was present in 24 granulosa cell tumors, although 1 granulosa cell tumor was tetrasomic for chromosome 12. Trisomy 12 was found in 27% (3 of 11) of the serous borderline tumors, but was not observed in any of the benign epithelial tumors (13 serous and 7 mucinous cystadenomas). These results confirm that trisomy 12 occurs in a significant proportion of fibromas. However, the incidence of trisomy 12 in granulosa cell tumors is far lower than suggested by previous studies. These results, in conjunction with those of previous cytogenetic reports, suggest that trisomy 12 is rare in benign epithelial ovarian tumors, but occurs fairly commonly as a sole anomaly in borderline epithelial tumors. Further investigation is necessary to establish the significance of trisomy 12 in the pathogenesis of these tumors.