PAX-2 is a transcription factor that controls the development of the kidney, organs deriving from the mesonephric (Wolffian) duct, and those related to the Müllerian duct. Although PAX-2 is shown to be a sensitive marker for tumors derived from these organs, but whether it is specific, that is, whether other tumor types also express PAX-2, has not been systematically evaluated in either primary or metastatic tumors. Tissue sections from 937 normal or reactive tissue samples, 759 primary neoplasms, and 332 metastatic neoplasms were submitted to PAX-2 immunostain. Among the non-neoplastic tissue, PAX-2 was expressed in glomerular parietal epithelial cells, renal collecting duct cells, atrophic renal tubular cells, epithelial cells of ovarian surface, fallopian tube, endocervix, endometrium, seminal vesicle, and lymphocytes. Among the primary neoplasms, PAX-2 was noted in 104/122 (85%) of renal cell carcinoma, 31/95 carcinomas of Müllerian origin, 17/17 (100%) lymphomas, 4/4 (100%) nephrogenic adenomas, and 1/16 (6%) benign parathyroid tumors, but was negative in 477 other tumors. Among the metastatic tumors, PAX-2 was noted in 70/95 (74%) metastatic renal cell carcinomas, 14/20 (70%) metastatic tumors of Müllerian origin, 1/20 (5%) metastatic colon carcinoma of lymph nodes, 1/62 (2%) metastatic breast carcinoma of lymph nodes, but was not seen in the remaining 247 metastatic tumors. PAX-2 expression in non-neoplastic mature tissue is limited to the organs whose embryonic development depends on this transcription factor. PAX-2 is a sensitive and specific marker for tumors of renal or Müllerian origin in both primary and metastatic contexts.