Retinoblastoma is the most common primary intraocular malignancy of childhood, occurring in about one out of 15,000 live births. A century ago, the mortality rate with this malignancy was nearly 100%; today, it is less than 10%. Furthermore, with recent advances in both diagnostic and therapeutic techniques, vision can often be preserved in one or both eyes. The approach to differential diagnosis utilized in the Wills Eye Hospital Ocular Oncology Service is outlined, and various diagnostic tests are described and illustrated. Procedures for examination under anesthesia are also detailed; it is emphasized that the physician should be prepared to institute appropriate treatment at the time of examination under anesthesia. Depending on the extent and nature of tumor involvement, treatment might consist of enucleation, external radiation, episcleral plaque irradiation, photocoagulation, cryotherapy, chemotherapy or a combination of these modalities. Indications, techniques and complications of each modality are discussed.