Although rare cases of PAX-8–positive primary lung carcinoma have been reported, details of staining distribution and intensity in such cases are limited. The aim of this study was to determine whether strong and diffuse PAX-8 staining can occur in primary lung carcinoma. Immunohistochemical staining for PAX-8 (Rabbit polyclonal, 10336-1-AP; Proteintech) was performed on whole-tissue sections from 418 resected primary lung carcinomas. PAX-8 was positive in 5/418 (1.2%) cases, all of which were large cell neuroendocrine carcinomas. Staining was weak to moderate in all 5 cases, and was seen in 5% to 30% of tumor cells. All other primary lung carcinomas (413/418) were negative for PAX-8. This study—the largest series of PAX-8-stained whole-tissue sections of primary lung carcinoma to date—shows that strong and diffuse staining for PAX-8 does not occur in primary lung carcinoma of any type. This staining pattern in a carcinoma in a lung specimen provides strong evidence of nonpulmonary origin.