Immunohistochemistry for transcription factor PAX8 (paired box gene 8) has recently emerged as a powerful tool in the differential diagnosis of gynecologic malignancies, especially when encountered at a metastatic site. Previous studies have shown PAX8 expression in the majority of ovarian and endometrial carcinomas; however, data regarding PAX8 expression in cervical tumors are limited. In this study PAX8 expression was evaluated in 136 epithelial malignancies of the uterine cervix-including 103 squamous cell carcinomas (SCC), 20 adenocarcinomas of usual type, 6 endometrioid adenocarcinomas, and 7 adenosquamous carcinomas-on tissue microarray slides. PAX8 immunopositivity was defined as at least weak nuclear staining in >5% of tumor cells. The majority of SCC were PAX8 negative (92%; 95/103), whereas among the endocervical adenocarcinomas PAX8 was positive in 70% (14/20) of the usual type and in 83% (5/6) of the endometrioid-type tumors. PAX8 expression was observed in 29% (2/7) of adenosquamous carcinomas. We conclude that PAX8 immunostain is negative in most cervical SCC and is less frequently expressed in endocervical adenocarcinomas as compared with the previously reported high sensitivity for ovarian and endometrial adenocarcinomas. When evaluating possible primary sites of a metastatic lesion, a negative PAX8 immunostain does not rule out common cervical epithelial malignancies.