The distinction between primary ovarian tumors and metastatic cancers to the ovary is frequently ambiguous. Recently, we reported that the D-14 monoclonal antibody (MAb), which is directed against a specific epitope of carcinoembryonic antigen (CEA), always reacts with colorectal adenocarcinomas and only rarely with neoplasms of non-gastrointestinal origin [J. Cancer Res. Clin. Oncol. 116, 51-56 (1990)]. We report here an analysis of the reactivity of four different anti-CEA MAbs with formalin-fixed tissue sections of human primary and metastatic colorectal and ovarian carcinomas. The four monoclonal antibodies employed were D-14, CEJ065, ZCEA1, and SP-625. D-14, CEJ065, and SP-625 MAbs reacted with essentially every colorectal adenocarcinoma. In contrast, ZCEA1 was the least reactive and 10 tumor samples showed no reactivity to this MAb. All four anti-CEA MAbs demonstrated scarce immunoreactivity with ovarian carcinomas and appear to be useful for distinguishing between ovarian carcinoma and colorectal metastasis to the ovary. Adenocarcinomas of the stomach and breast were also examined to determine CEA reactivity with the D-14 MAb, since these tumors need to be considered in the differential diagnosis of an ovarian mass. The majority of stomach adenocarcinomas were immunoreactive. In contrast, only 3 of 36 breast carcinomas were weakly immunoreactive, indicating that D-14 MAb is of no assistance in identifying breast carcinoma metastasis to the ovary.