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Retinoblastoma is a very rare disease in adults. We are reporting a rare case of resistant retinoblastoma in 23-year-old patient. A 23-year-old male patient presented with loss of vision in the right eye over one-month duration. Examination showed an epiretinal membrane in the right macula in addition to a white mass located inferiorly and associated with vitreous seeds. The diagnosis of retinoblastoma was established. In order to save the patient′s life and to preserve the eye and vision, he was treated with chemotherapy, focal therapy, and radioactive Iodine 125 plaque therapy. The tumor was resistant for treatment and recurred two years after plaque therapy, and enucleation showed well-differentiated retinoblastoma. Retinoblastoma may present in adults, and it was resistant to both chemotherapy and plaque radiation therapy in our case.