Maspin has been demonstrated to be a suppressor of invasion and cell motility in vitro, whereas in vivo analyses have reported that increased expression of maspin is associated with malignant behavior. The present study examined maspin expression in normal lung and non-small-cell lung cancers. Only proximal airway cells in the normal lung expressed maspin, and the expression was associated with decreased methylation. This association was also observed in non-small-cell lung cancers, but the expression was quite different among histologic subtypes; 20 of 21 squamous cell carcinomas showed intense, uniform expression, whereas the expression status varied among adenocarcinomas. Of the 119 adenocarcinomas, 60 were negative, 23 positive and 36 showed a heterogeneous expression pattern. The expression was inversely correlated with markers of peripheral airway cells. Taken together, the results suggest that maspin may be expressed in association with the proximal airway cell type. It is of note that the heterogeneous expression pattern of maspin is quite distinctive, showing geographic positivity in the individual tumors. Separate analysis of methylation status in positive and negative portions of individual tumors provided an instance of intratumor diversity associated with promoter DNA methylation.