The purpose of this retrospective study is to investigate the influence of 45 Gy megavoltage external beam radiotherapy on the occurrence of second primary tumours in hereditary- and non-hereditary retinoblastoma patients. Eighty-seven hereditary and 19 nonhereditary patients were irradiated for retinoblastoma. The follow-up of the hereditary patients ranged from 4–23 years (mean 12.4 years), of the non-hereditary patients from 6–23 years (mean 12 years). In the hereditary group 4 patients developed a second primary tumour (2 rhabdomyosarcoma, 1 osteosarcoma, 1 malignant histiocytoma), and 5 patients developed a pineoblastoma. Three second primary tumours were situated inside the radiation field. The latency period ranged from 1.5 to 18 years (mean 4.8 years). None of the non-hereditary patients developed a second primary tumour. The actuarially calculated probability of being free from second primary tumours was 96.9% at 10 years and 89.4% at 20 years (pineoblastoma excluded). The survival was 91.2% at 10 years and 84.2% at 20 years (pineoblastoma excluded). From this study it is suggested that external beam irradiation has a potentiating effect in patients, with the genetic predispopsition for retinoblastoma and who are more susceptible to second primary malignancies.