Aberrations of the components of the Rb pathway have been frequently reported in HCC: CDK4 overexpression was found in 73% of cases (17), RB1 gene alterations and absence of p-Rb expression were detected in ~4–20% and 28% of cases, respectively (18, 19), whereas inactivation of the CDK inhibitor p16INK4a emerged in 22% (18), 64% (19), or 58% (20) of patients. The gene discussed is RB1; the disease is hepatocellular carcinoma.