Tumor-specific antigens are usually defined by monoclonal antibodies (MAbs) and can play critical roles in the diagnosis and therapy of carcinomas. Despite advances in the understanding of the molecular genetics of human prostate carcinomas, therapeutic approaches require that tumor-specific markers, preferably on the cell surface, should be defined. In this study, we examined the expression of an oncofetal antigen tumor-associated glycoprotein-72 (TAG-72) in prostatic adenocarcinomas with a Gleason grade of six or higher. Using a second generation MAb CC49 against TAG-72, immunoreactivity was detected in 88% (29/33) of the prostatic cancer tissues. Occasionally, the benign epithelium showed a very faint immunostaining but in most of the specimens, no reactivity was detected. Positive staining was present in the cytoplasm and the cell membrane of the malignant cells similar to reports on other cancer tissues. A weaker staining pattern of this antigen was seen in poorly differentiated areas. A significant negative correlation (r = -0.36, p < 0.05) was observed between TAG-72 antigen expression and Gleason grade. The TAG-72 antigen expression in prostatic adenocarcinomas may be used as a target for radioimmunotherapy by the multivalent single chain antibody CC49 constructs recently generated by our group.