Tumor-specific antigens are important in the study of tumor biology, tumor diagnosis and prognosis and possibly in tumor therapy. We demonstrate in this report that surgical specimens of colon, breast and ovarian tumors in native-state in vitro gel-supported three-dimensional in vitro histoculture maintain in vivo-like expression of the important tumor antigens TAG-72 and CEA. These results are in contrast to previously-reported studies indicating lack of expression of TAG-72 in monolayer cultures. Our knowledge and utilization of tumor-specific antigens, including the potential for therapy and predicting individual sensitivities could be enhanced in studies using in vitro three-dimensional gel-matrix histoculture for human tumors.