A 62-year-old man with a large ciliochoroidal melanoma developed early-onset scleral necrosis with tumor extrusion within 1 month of epibulbar iodine I 125 plaque radiotherapy. The eye was enucleated. Pathologic study revealed nonmicrobial scleral necrosis with extrusion of histologically intact and necrotic uveal melanoma cells. The patient has been followed up for 15 months without clinical recurrence. We discuss possible mechanisms to explain the early development of scleral necrosis after plaque therapy in this patient.