Expression of the Wilms' tumor gene WT1 in de novo lung cancer was examined using quantitative real‐time RT‐PCR and immunohistochemistry. Overexpression of the WT1 gene was detected by RT‐PCR in 54/56 (96%) de novo non‐small cell lung cancers examined and confirmed by detection of WT1 protein with an anti‐WT1 antibody. Overexpression of the WT1 gene was also demonstrated in 5/6 (83%) de novo small cell lung cancers by immunohistochemistry. Furthermore, when the WT1 gene was examined for mutations by direct sequencing of genomic DNA in 7 lung cancers, no mutations were found. These results suggest that the nonmutated, wild‐type WT1 gene plays an important role in tumorigenesis of de novo lung cancers and may provide us with the rationale for new therapeutic strategies for lung cancer targeting the WT1 gene and its products. © 2002 Wiley‐Liss, Inc.