By investigating the genetic backgrounds of patients with de novo combined SCLC/NSCLC as well as those who experienced SCLC transformation from lung adenocarcinoma after TKI treatment, Lin et al. reported a high consistency in EGFR/TP53/RB1 mutations and expression patterns of p53 and Rb in these two different histologic components of SCLC, indicating that inactivation of TP53/RB1 function might be an early event in the histogenesis of synchronous and metachronous SCLC/NSCLC [61]. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.