Although conjunctival squamous cell carcinoma is known to develop as a result of chronic irritation from wearing an ocular prosthesis, orbital sebaceous gland carcinoma arising in an anophthalmic pocket is extremely rare. We report a 68-year-old female who developed a sebaceous gland carcinoma 65 years after her right eye was enucleated (at the age of three years) due to congenital glaucoma. The patient had noticed increasing discharge and swelling of her right eyelid. Incisional biopsies of an underlying orbital mass revealed poorly differentiated sebaceous gland carcinoma. The sebaceous gland carcinoma in this case could have been caused by chronic irritation as a result of long-standing use of a poorly fitted ocular prosthesis. The current case of a malignant tumor occurring 65 years after enucleation emphasizes the importance of long-term clinical surveillance to monitor for tumor formation. Careful examination of the anophthalmic socket should be part of the physical examination.