PAX-8 is expressed in the thyroid, non-ciliated mucosal cells of the fallopian tubes and simple ovarian inclusion cysts, but not normal ovarian surface epithelial cells. PAX-8 is expressed in ovarian serous, endometrioid, and clear cell carcinomas, but only rarely in primary ovarian mucinous adenocarcinomas. Over 98% of clear cell RCCs, 90% of papillary RCCs, and 95% of oncocytomas were positive for PAX-8. Similarly, the absence of expression of PAX-8 in breast and other non-GYN carcinomas other than those primary to the thyroid indicates that PAX-8 is an important new marker of ovarian cancer and a useful marker for the differential diagnoses in lung and neck tumors, or tumors at distant sites where primary lung carcinoma or thyroid carcinoma are possibilities. PAX-8, combined with organ system-specific markers such as uroplakin, mammaglobin, and TTF-1 can be a very useful panel to determine the primary site of invasive micropapillary carcinomas of ovary from bladder, lung, and breast. Unlike the polyclonal anti-PAX-8 antibody, the ZR1 rabbit monoclonal antibody does not react with pancreatic neuroendocrine tumors, thymic tumors, and lymphocytes.