Here, by performing targeted next-generation sequencing (NGS) on 241 cancer genes followed by histopathologic and clinical analyses, KEAP1-inactivating mutations were found in 31% of the cases in conjunction with other NSCLC-type alterations of KRAS, STK11, and NFE2L2 genes, a molecular signature commonly found in the adenocarcinoma subtype. Here, KEAP1 is linked to cancer.