We were intrigued by reports showing that p107-deficient mice with Rb deletion in the developing retina (Chx10Cre; Rblox/−; p107−/−) develop non invasive retinoblastomas with low penetrance, whereas similar mice with an additional retina-specific loss of p53 (Chx10Cre; Rblox/−; p107−/−; p53Lox/−), or with decreased p107/p130 levels (Chx10Cre; Rblox/lox; p107+/−; p130−/−), develop aggressive and invasive bilateral retinoblastomas [12], [13]. The gene discussed is RBL2; the disease is retinoblastoma.