Being a tumor-suppressor gene, RB1 germline inactivation in patients previously diagnosed with hereditary RB has up to 20 times higher susceptibility to develop subsequent malignant neoplasms (standardized incidence ratio (SIR) = 20.4 (confidence interval (CI) 15.6–26.1)) (SMN) [2,3,4,5,6], and the risk of presenting a third neoplasm after a second is up to 8 times higher compared to the general population risk (SIR = 8.5 (CI 3.7–16.7)) [7,8]. The gene discussed is RB1; the disease is retinoblastoma.