BACKGROUND High‐grade prostate intraepithelial neoplasia (PIN) is the most likely precursor of prostate adenocarcinoma. However, the relationship between this lesion and prostate cancer has not yet been established. The detection of cytogenetic changes in the lesions prior to prostate adenocarcinoma would be useful in demonstrating such a pathogenic relationship. METHODS Twenty eight high‐grade PIN cases were found among 57 specimens of radical prostatectomy performed for clinically localized prostate cancer. Fluorescence in situ hybridization (FISH) analysis using centromeric probes to enumerate chromosomes 7, 8, 10, and 12 was performed to study the numerical chromosome alterations. FISH analysis was carried out over isolated nuclei obtained from high‐grade PIN areas and prostate cancer foci in the same prostatectomy specimen. RESULTS Of the 28 suitable cases it was possible to complete the study in 26 tumor and 20 PIN areas. The remaining cases were excluded because of insufficient tissue or poor preservation. Cytogenetic alterations (aneuploidy) were found in 16 of the 26 (62%) tumors studied. The most frequent chromosome alteration was trisomy 7, detected in 12 (75%) aneuploid tumors, followed by monosomy 8 present in 5 (31%) aneuploid tumors. Trisomy 7 was also the most frequent isolated chromosome alteration since it was detected in 7 (44%) tumors. Thirteen of 20 (65%) PIN cases were aneuploid when studied by FISH. Trisomy 7, trisomy 8, and monosomy 8 were the most common cytogenetic alterations in the 20 PIN areas studied, being observed in nine (45%), six (30%), and four (20%) cases, respectively. FISH analysis showed a high correlation (75% cases) in ploidy and pattern of cytogenetic alterations between high‐grade PIN areas and the paired prostate cancer focus in the same specimen. CONCLUSIONS The above results show a cytogenetic link between high‐grade PIN and prostate cancer, suggesting that the former could be an early form of prostate cancer. Prostate 47:29–35, 2001. © 2001 Wiley‐Liss, Inc.