Napsin A is a novel peripheral airway epithelial marker that, because it is commonly expressed in lung adenocarcinomas but absent in squamous cell carcinomas, is considered to be useful in distinguishing between these 2 types of tumors. Recent immunohistochemical studies, however, have reported napsin A expression in up to 26% of squamous cell carcinomas of the lung, a finding that indicates that this marker may not be as specific for lung adenocarcinomas as is generally believed. To determine the causes of the discrepancies between some recent immunohistochemical studies and previous reports on napsin A expression in squamous cell carcinomas of the lung, 90 pulmonary and 64 nonpulmonary squamous cell carcinomas (20 skin, 10 esophagus, 7 uterine cervix, and 27 from the head and neck region) were investigated by immunohistochemistry for this marker. None of the 90 squamous cell carcinomas of the lung exhibited napsin A positivity in the neoplastic cells; however, because strong napsin A reactivity was observed in hyperplastic type II pneumocytes and in intra-alveolar macrophages, both of which were sometimes seen entrapped within the tumor, it has been concluded that the presence of these entrapped cells was the most likely cause of the discrepancies. Pathologists should be aware of this potential pitfall in the interpretation of the immunostaining for napsin A, especially when small lung biopsy specimens, tissue microarrays, or cytology specimens are being evaluated.