Having previously established gamma-glutamyltransferase (GGT) as a marker of experimental carcinogenesis in rat liver, we investigated whether human tumors differ from their tissue or origin by showing a higher activity or different localization of this enzyme histochemically. We found such differences in each of the human carcinomas we examined. The presence of GGT activity in carcinomas arising in organs normally containing little (tongue) or no GGT activity (larynx, urinary bladder, and esophagus) clearly distinguished cancerous from normal epithelium. In the breast, colon and prostate, GGT activity was normally present in a defined anatomical distribution bordering luminal surfaces. Carcinomas arising from these tissues showed a loss of the normal pattern of activity and contained cells with almost homogenous GGT activity in the cytoplasm. Such differences clearly distinguished carcinomatous from normal epithelium in these organs. The increased GGT activity observed in all nine carcinomas arising from seven different organs suggests that GGT may be a common marker of human epithelial tumors and staining for GGT may become a useful tool in the detection of human epithelial neoplasms.