Aneusomy of the Y chromosome was examined in paired malignant and benign prostate tissue from 31 radical prostatectomy specimens to analyze the possible relationship between Y chromosome loss and disease status, and to define its relationship to the aging process. Tissues from men aged 45-55 years or 56-75 years at the time of prostate cancer diagnosis were examined for Y chromosome dosage using Polymerase Chain Reaction (PCR) and Fluorescence In Situ Hybridization (FISH) techniques.PCR analysis of malignant tissue demonstrated Yp sequence losses in 0 % (0/20) of men aged 45-55 years and 18% (2/11) of men aged 56-75 years; no losses were observed in benign epithelium from either age group. FISH analysis demonstrated Y chromosome loss in 5% (1/20) of malignant tumors, 14% (1/7) of prostatic intraepithelial neoplasia (PIN) lesions, and 0% (0/20) of benign glands in men aged 45-55 years, and in 18% (2/11) of malignant glands, 50% (1/2) of PIN lesions and 9% (1/11) of benign glands in men aged 56-75 years. Interestingly, focal loss of the Y chromosome involving multiple or single malignant glands was observed by FISH analysis in 25% (5/20) of men aged 45-55 years and 1/11 (9%) of men aged 56-75 years. These results indicate that Y chromosome loss is associated with both the aging process and malignancy in the prostate.