Background:Clear cell acanthoma is a rare solitary benign epidermal tumor of unknown etiology. The disease arises in the middle-age, with no sex predominance. It appears as a single reddish papule or papule-nodule and a peripheral scaling collarette is characteristic. Although solitary lesions are the rule, less than 30 cases of multiple Clear cell acanthoma have been described in the literature to date.Main observations:We report an unusual case of a healthy 74-year-old male with multiple clear cell acanthoma on the lower extremities treated successfully with cryotherapy.Conclusions:Despite significant progress in treatment of clear cell acanthoma, cryotherapy, based on liquid nitrogen, remains an important alternative in treating multiple clear cell acanthomas.