Purpose: To evaluate the results of trans-pupillary diode laser thermotherapy and exo-cryotherapy combined with systemic chemotherapy for the treatment of retinoblastoma. Methods: Thirty-seven children with retinoblastoma received 2 to 6 cycles of systemic chemotherapy. Fifteen eyes with small- to medium- sized tumors were treated with thermotherapy and 5 eyes had additional cryotherapy. Thermotherapy was delivered for posterior tumors. Each tumor was treated separately with a continuous mode diode laser using an indirect ophthalmoscope delivery system. Peripheral tumors were treated by exo-cryotherapy. Results: Posterior tumors less than 10 disc diameter in size responded well to thermotherapy. From one to four laser sessions were needed to control tumors. Two eyes with peripheral diffuse tumors relapsed after initial control. 83.78% of patients were treated without external beam radiation. Conclusion: Trans-pupillary thermotherapy and exo-cryotherapy is an effective technique to treat small- to medium- sized posteriorly located retinoblastoma in children, avoiding external beam irradiation in many cases. Early treatment and close follow-up is recommended for these eyes.