Ellison et al. (2006) previously suggested nutlin-3a as an efficient treatment to induce p53-dependent apoptosis and p21-dependent cell cycle arrest in in vitro retinoblastoma cell lines. In agreement, our study confirms the efficient activation of the p53 pathway, with the involvement of PUMA in inducing apoptosis and p21-mediated cell cycle arrest, in both retinoblastoma cell lines tested. These results suggest drug efficacy in metastatic and non-metastatic tumors, as represented by the Y79 and Weri-Rb1 cell lines, respectively (Chévez-Barrios et al., 2000). This evidence concerns the gene TP53 and retinoblastoma.