Napsin A is a human aspartic proteinase found primarily in type II pneumocytes, alveolar macrophages and in the renal proximal tubules. Napsin A is more sensitive and specific in detecting lung adenocarcinomas than TTF-1. Differentiation of NSCLC into histologic types is important with the emergence of new targeted therapies. Literature suggest that a panel consisting of Napsin A, TTF-1, p63 and CK 5/6 is useful in distinguishing lung adenocarcinoma from squamous cell carcinoma. Napsin A is also useful in differentiating primary lung tumors from metastatic tumors except in the case of metastasis from the kidney. In addition, Napsin A may also be reactive to a small percentage of thyroid and endometrial ca. On the contrary, circulating levels of Napsin A are increased in patients with idiopathic pulmonary fibrosis but is not elevated in pulmonary adenocarcinoma or renal dysfunction. A multivariate analysis demonstrates that absence of Napsin A is an independent prognostic factor for reduced survival time in surgically resected lung adenocarcinomas.