Rekhtman and colleagues performed NGS of 45 histologically pure LCNECs and identified two major subsets: a SCLC-like subset (40%) with concurrent alteration of tumor protein p53 (TP53) and RB1, and an NSCLC-like subset (56%), lacking RB1 and TP53 co-alteration and characterized by NSCLC typical mutations such as serine/threonine kinase 11 (STK11), Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (characteristic of LUAD), and kelch-like ECH associated protein 1 (KEAP1) mutations (typical of both LUAD and LSCC) [14,23,24,30]. Here, RB1 is linked to small cell lung carcinoma.