Ovarian carcinoma has a high mortality rate, because most ovarian carcinomas are detected at a late stage. Traditional therapies, such as surgical debulking and chemotherapy, have not been successful in improving the long-term survival of these patients. Alternative therapies targeting various biomarkers, such as carcinoembryonic antigen (CEA), Tag-72, and Lewis-Y antigen, have been developed to treat patients with advanced ovarian cancers. To ensure that therapies targeting these biomarkers are effective, it is imperative to determine whether there is any differential expression of these targeted biomarkers between primary and metastatic ovarian carcinomas. In the present study, primary and metastatic lesions from 68 and 58 patients, respectively, including primary and matched metastatic lesions from 31 patients, were evaluated for cytoplasmic and membranous expression of CEA (clone Col-1), Tag-72 (clone CC-49), and Lewis-Y antigen (clone BR-96) by immunohistochemistry. No significant differences were observed with cytoplasmic and membranous expression of Tag-72 (CC-49) and Lewis-Y antigen (BR-96) in the primary and metastatic, matched and unmatched lesions (Wilcoxon signed-rank test). Although there was no statistically significant difference in the scores of CEA (Col-1) between primary and metastatic lesions, 5 of 11 (45%) cases with positive staining with CEA (Col-1) demonstrated discordant results between primary and metastatic lesions. There was a moderate positive correlation of the cytoplasmic and membranous expression of Tag-72 (CC-49), as well as cytoplasmic expression of BR-96 between primary and metastatic ovarian carcinomas. There was a weak negative correlation between the membranous expression of CEA (Col-1) and that of Lewis-Y antigen (BR-96); however, the difference was not statistically significant. No correlation was observed with other combinations of biomarkers. Our findings suggest that samples from either primary or metastatic ovarian carcinomas can be used for the evaluation of the expression of Tag-72 (CC-49) and Lewis-Y antigen (BR-96) to identify targets for novel therapies in patients with disseminated ovarian carcinomas. CEA (Col-1), due to its low expression and variation in phenotypic expression between primary and metastatic lesions, should be evaluated carefully in metastatic lesions before targeting the CEA antigen with CEA (Col-1)-like antibodies. © 2003 Elsevier Inc. All rights reserved.