To date, there is no reliable immunohistochemical marker that discriminates between primary pulmonary squamous cell carcinoma (SCC) and cervical SCC metastatic to the lung. In this study, immunohistochemical staining of p16 was performed on 33 primary pulmonary SCCs, 48 primary cervical SCCs, and 17 cases of cervical SCC with pulmonary metastasis. Expression of p16 was noted in 47 cases of cervical SCC (47/48 [98%]), and all were strongly stained. Of the 7 cases of primary pulmonary SCC (7/33 [21%]) in which p16 expression was detected, 3 were weakly positive, 1 was moderately positive, and 3 were strongly positive. Among these p16+ pulmonary SCCs, only 1 showed detectable human papillomavirus DNA. Of the 17 cases of cervical SCC with pulmonary metastasis, all of the pulmonary and cervical tumors were positive for p16. p16 is a useful marker for the discrimination between cervical and pulmonary SCCs. The performance of p16 staining at different cutoff values was also compared.