Keratoacanthoma of the lower eyelid developed in two patients. In the first case, conventional excision biopsy necessitated a large eyelid reconstruction procedure. In the second case, 5-fluorouracil was injected into the base of the keratoacanthoma. Both treatments resulted in complete resolution of the lesion with excellent cosmesis. Thus, intralesional 5-fluorouracil can be useful for keratoacanthomas of the eyelid in patients who are not good candidates for surgery.