Serum positivity to an antigen recognized by the monoclonal antibody (MAb) which will be administered is frequently being used as a predictive criterion for positive MAb tumor localization. In the present study, which is based on our previous data that clearly showed no correlation between quantitative levels of CEA in sera and in carcinoma tissues, we selected a population of 12 primary colorectal carcinoma patients which were serum CEA-negative. The main purpose was to assess the potential diagnostic use of Radioimmunoguided Surgery (RIGS) with an anti-CEA FO23C5 F(Ab')2 MAb and its clinical value in this series of patients. In all RIGS patients, the MAb localized to histologically confirmed tumor; this included 96% of primary tumor tissues, 29% of lymph nodes and one occult liver metastasis. Thus, serum CEA positivity should not be a criterion for the use of anti-CEA MAbs for the diagnosis of colon cancer, since the serum CEA level is not indicative of CEA expression in tumors.