With regard to the tricky treatment choice, recent data suggest that RB1 expression could represent a potential biomarker to select the best treatment for LCNEC patients (RB1 loss should guide toward SCLC-chemotherapy; on the other hand, LCNEC showing intact RB1 expression should be treated with NSCLC-regimens) (15, 16). This evidence concerns the gene RB1 and large cell neuroendocrine carcinoma.