Dermatofibromas are benign skin lesions that may be treated if symptomatic or for cosmetic concerns. We present a case of an African American woman with an enlarging, pruritic dermatofibroma on the thigh that was treated with fractionated carbon dioxide (CO2) laser three times approximately 5 weeks apart. Between laser treatments, topical corticosteroids were applied to the lesion for a total of 13 weeks. The dermatofibroma completely flattened and became asymptomatic within 1 month after the final laser treatment. We hypothesize that the fractionated CO2 laser ablated a portion of the stromal component of the lesion and introduced microscopic channels that facilitated deeper penetration of the topical corticosteroids into the lesion. This is the first reported case demonstrating the successful treatment of a symptomatic dermatofibroma using combination therapy with fractionated CO2 laser and topical corticosteroids.