Hereditary retinoblastoma patients are at an increased risk for subsequent primary tumors after successful treatment for their initial cancer. Two mechanisms may be responsible for this increased incidence of second malignancies: genetic susceptibility (RB1 gene alterations) and induction by radiation that is frequently used as treatment for retinoblastoma. Because of the high cure rates obtained in the treatment of retinoblastoma, the risk of subsequent primary tumors is substantial, especially in the radiation field. We present four retinoblastoma survivors who developed multiple subsequent primary tumors. Two retinoblastoma survivors developed one and the other two patients two subsequent primary tumors. Despite extensive treatments two patients died of their second primary tumor in the head and neck region. The head and neck surgeon has an increasingly important role in the diagnosis and management of subsequent primary tumors in retinoblastoma survivors.