Keratoacanthoma is a rapidly-growing tumor, which histologically resembles squamous cell carcinoma. Although it may regress spontaneously, keratoacanthoma is routinely treated by excision. Although excisional surgery is the treatment of choice, this can result in functional and cosmetic defects when large or strategically located lesions are treated. An effective nonsurgical treatment would be desirable in such cases. We report two cases of giant keratoacanthoma treated with intralesional methotrexate. Each case showed complete resolutions over 6 injections within 10 weeks. No recurrence occurred during the followup period. We suggest that intralesional injection of methotrexate is an effective and non-operative modality for the treatment of giant keratoacanthoma. (Korean J Dermatol 2006;44(7):902∼905)