With the knowledge that pRb is 95% wild-type in BRAF mutant melanoma [27] coupled with our discovery that all examined stage IV BRAFV600E-mutant melanoma tissues express nuclear hyperphosphorylated pRb-Ser780 reasons that blockade of the CDK4/6-cyclin D1 pathway should lead to active hypophosphorylated pRb, thus causing cell cycle arrest. The gene discussed is CDK4; the disease is melanoma.