It was reported recently that RB pathway ablation in combination with three other genetic alterations in human melanocytes (NRAS activation, p53 activation and hTERT expression) is necessary and sufficient to produce melanoma-like lesions in a reconstituted skin-xenograft model (Chudnovsky et al, 2005), in good agreement with our genetic model (Bennett, 2003). The gene discussed is RB1; the disease is melanoma.