PAX2 and PAX8 are transcription factors that are essential in embryonic development of mullerian organs. They may also play a role in tumor development in these organs. The diagnostic utility of PAX2 and PAX8 relative to one another has not been comprehensively studied. Archival tissue samples for normal or non-neoplastic tissue (251), primary epithelial neoplasms (316 for PAX2 and 357 for PAX8), and metastatic epithelial neoplasms (16), all of mullerian origin, were subjected to PAX2 and PAX8 immunostaining. The staining frequency, extent, and intensity for these markers were compared. Virtually identical PAX2 and PAX8 expressions were noted in nonneoplastic tissue. They were constantly seen in most epithelial cells (but not in stromal cells) of the endocervix, endometrium, fallopian tube, paratubal cyst, endosalpingiosis, endometriosis, and endometrial polyp. Within the primary epithelial neoplasms, PAX2 and PAX8 expression was noted in 55% and 98% of serous tumors, 25% and 94% of endometrioid tumors, 19% and 100% of clear cell tumors, 11% and 67% of transitional/undifferentiated tumors, and 10% and 22% of mucinous tumors, respectively. Regardless of histologic subtypes, PAX2 staining was noted in fewer cells and with less staining intensity compared with PAX8. No tumor showed only PAX2 staining. Within the metastatic carcinomas, PAX2 and PAX8 expression was noted in 38% and 98% of cases, respectively, with a diffuse and strong staining for PAX8, contrasting with a patchy and weak PAX2 expression. PAX2 and PAX8 are constantly expressed in normal or non-neoplastic tissue of mullerian origin. For primary and metastatic mullerian epithelial tumors, PAX8 shows strong and diffuse staining in most cases of all histologic subtypes, except in mucinous tumors. In contrast, PAX2 expression is always less than PAX8, and exclusive staining for PAX2 is not seen. PAX8 supersedes PAX2 as probably the best epithelial marker hitherto for primary or metastatic mullerian epithelial tumors.