Against the background to develop novel mechanism-based approaches using retinoids in the prospective treatment of retinoblastoma, in the present study we set out to determine the effects of exogenous RA and combined RA/BMP-4 application on WERI-Rb1 retinoblastoma cell viability and apoptosis and to elucidate signaling mechanism underlying these effects, including the involvement of RARs and RXRs, specific RA receptor subtypes and caspases. This evidence concerns the gene RARS1 and retinoblastoma.