Immunohistochemical methods were used to study the expression of prostate-specific antigen (PSA) in more than 400 samples of normal and pathological human tissues, including the female and male breast, male and female prostate (Skene's gland), and selected other tissues. In the normal female and male breast, no immunohistochemical positivity of PSA was observed in epithelial structures. In contradistinction to normal breast, normal male and female prostate tissue exhibited regular and marked PSA positivity. Variable expression of PSA was observed in membranes of adipocytes in breast tissue and axilla, apocrine sweat glands, endothelium of small vessels, gastric parietal cells, and some further rare normal extraprostatic tissue components. Unlike normal breast tissue, apocrine rnetaplasia in benign female breast disease and in male gynecomastia displayed distinct positivity for PSA. In cancerous female breast, expression of PSA decreased with the decreasing degree of differentiation. High expression was recorded in the signetring cell variant of ductal female breast carcinoma. If we disregard the absence of expression of PSA in the normal breast and its minimal and variable PSA expression of some normal extraprostatic structures, it is evident that in the female, similarly as in the male, the prostate is the principal source of PSA. In cases of discussed pathological breast tissues and other pathological tissues known to produce PSA, the total amount of PSA is the summation of normal prostatic and anomalous extraprostatic pathological tissue production in the male and female patient. (The J Histotechnol 23:105, 2000)