A novel tumor marker, tumor-associated glycoprotein-72 (TAG-72), has been identified using monoclonal antibody (MAb) B72.3. Using immunohistochemical techniques, TAG-72 has been found in carcinomas of various origin including colon, stomach, breast, lung, prostate, and ovary, as well as in body fluids. The presence of TAG-72 in serum samples from 260 patients with colorectal disease (malignant or benign) has been evaluated using the CA72-4 assay. Approximately 40% of patients with colorectal cancer exhibit elevated levels of this marker; moreover, the presence of positive levels of TAG-72 significantly correlates with advanced stages of disease, suggesting that TAG-72 may be a good marker of advanced colorectal cancer. Only 2% of the patients diagnosed with colorectal disease had elevated TAG-72 serum levels indicating the high specificity of this marker. A comparative study with carcinoembryonic antigen (CEA) serum levels showed a complementarity of the two tumor markers; in fact, 49.6% of CEA negative cases scored positive for TAG-72. A longitudinal evaluation of TAG-72 serum levels in 31 patients with malignant disease was performed. The results indicate that patients with increasing TAG-72 serum levels postoperatively may be indicative of recurrent disease. In 60% of patients in which significant changes of CEA levels could not be detected, TAG-72 showed rising positive levels prior to clinical evidence of recurrent disease. These results suggest that the simultaneous use of TAG-72 and CEA serum markers may be useful in the diagnosis of recurrent disease and therefore play an important role in the clinical management of cancer patients.