The aim of the present study was to compare the usefulness of the peripheral airway cell markers, naspin A and surfactant protein A (SP-A), for distinguishing primary lung adenocarcinoma from adenocarcinomas of other organs in various clinical conditions. Immunohistochemical expression of napsin A and SP-A was analyzed at primary sites of 120 lung carcinomas and 40 adenocarcinomas of other organs, at lung metastatic sites of 32 adenocarcinomas of other organs, and in metastatic lymph nodes of 21 lung adenocarcinomas and 45 adenocarcinomas of other organs. Napsin A and SP-A expressions were compared between primary and recurrent sites in 8 lung adenocarcinomas. Napsin A and SP-A expressions were noted in 84.3% and 53.0% of primary sites of 83 lung adenocarcinomas, respectively, but neither napsin A nor SP-A was expressed at primary sites of other histological types of lung carcinomas or at primary or metastatic sites of adenocarcinomas of other organs. In lung adenocarcinomas, napsin A and SP-A were expressed in metastatic lymph nodes in 81.0% and 19.0%, respectively, and at recurrent sites in 87.5% and 37.5%, respectively. Napsin A is superior to SP-A for distinguishing primary lung adenocarcinoma from adenocarcinomas of other organs at primary, metastatic, and recurrent sites.