In this report, we show that the addition of an efficiently expressed transgene encoding normal or mutant human MYC can convert weakly tumorigenic human PNEC cells, derived from a human ESC line and depleted of tumor suppressors RB1 and TP53, into highly malignant, metastatic SCLC-like cancers after implantation into the renal capsule of immunodeficient mice. Here, RB1 is linked to cancer.