The differentiation of ovarian metastases from colonic carcinoma and primary ovarian carcinoma can be difficult. To assess the utility of cytokeratin 7 and cytokeratin 20 immunostains in this setting, we studied routinely processed, formalin-fixed tissue from 165 ovarian tumors, including 45 serous carcinomas, 40 mucinous carcinomas, 64 endometrioid carcinomas, and 16 metastatic colonic adenocarcinomas with an avidin-biotin immunohistochemical technique. A cytokeratin 7+/cytokeratin 20- immunophenotype was seen in 86% of the endometrioid carcinomas, 27% of the mucinous carcinomas, 40% of the serous carcinomas, and none of the metastatic colorectal carcinomas. Conversely, a cytokeratin 7-/cytokeratin 20+ immunophenotype was seen in 94% of the metastatic colonic tumors, 5% of the mucinous carcinomas, and none of the endometrioid or serous tumors. We concluded that cytokeratin immunostains can be helpful in distinguishing metastatic colonic adenocarcinoma from primary ovarian carcinomas, particularly endometrioid carcinomas. Rare ovarian mucinous carcinomas may show the same immunophenotype as metastatic colonic carcinomas.