Genomic and transcriptomic analyses of a cohort of 75 LCNECs suggested the subclassification into two major molecular subtypes: type I LCNEC (37%), characterized by biallelic TP53 and STK11 or KEAP1 alterations and neuroendocrine phenotype, and type II LCNEC (42%), harboring biallelic TP53 and RB1 inactivation. This evidence concerns the gene KEAP1 and large cell neuroendocrine carcinoma.