We report an aggressive keratoacanthoma of the upper eyelid that recurred at the site of a previously excised keratoacanthoma. The diagnosis was confirmed by biopsy. Because the surgery required would be extensive, medical therapy was tried first. The tumor was treated with intralesional injections of 5-fluorouracil and radiotherapy. Despite this therapy, the orbital computed tomogram showed tumor extension into the orbit, and an orbital exenteration was performed. Histopathology of the excised tumor was consistent with squamous cell carcinoma. We discuss the topic of malignant transformation of the keratoacanthoma.