AbstractKlein et al. have demonstrated that basal cell carcinoma responds favorably to topical applications of 5‐fluorouracil in an aquaphor creme base. In the present study 53 patients with advanced cutaneous basal cell and epidermoid carcinoma were treated with 5, 10, or 20 percent 5‐fluorouracil (5‐FU) in an aquaphor creme base to determine whether this mode of therapy might be superior to surgical excision or irradiation therapy. Patients included in the study fulfilled at least one of the following criteria on which the diagnosis of advanced cutaneous malignancy was made: (1) Primary epidermoid or basal cell carcinoma of the skin—(a) 2.0 cm in diameter or larger, or (b) involving deeper structures such as cartilage on the ear or bone on the top of the head, or (c) occurring in an area that would require a major surgical procedure to cure, or (d) requiring extensive irradiation therapy to cure. (2) Recurrent lesion at a site where a previous malignant lesion had been adequately treated. (3) Repeated solitary lesions occurring at different anatomic sites. (4) Multiple lesions, at least one of which was malignant, occurring simultaneously over a wide cutaneous area. The appropriate concentration of 5‐FU creme was applied once daily for a minimum of 6 weeks and an average period of 9 weeks. One patient with a Marjolin's ulcer was treated in the hospital, and the remainder were treated on an outpatient basis. Pathologic diagnosis were as follows: basal cell, 35; epidermoid, 9; carcinoma in situ, 4; basal cell and epidermoid in the same patient, 3; and basosquamous, 2. In 50 patients progressive inflammation, gradual regression, disappearance, and healing were noted. Only malignant and premalignant tissue and its stroma appeared to be affected, while normal skin was affected only slightly or not at all. Healing occurred primarily with minimal or no scar formation. No local or invasive sepsis occurred. In three patients an apparently adequate inflammatory response was achieved, but the primary disease process was not eradicated; two of these patients had epidermoid carcinoma and one had basal cell carcinoma. Except for one patient who has been followed for 2 months since completing chemotherapy, the post‐treatment follow‐up period has ranged from 4 months to 2 years. The average follow‐up period is 9 mouths. These preliminary results seem to indicate that daily topical application of an appropriate concentration of 5‐fluorouracil in an aquaphor creme base for at least 6 weeks to advanced cutaneous basal cell or epiderrnoid Carcinoma is the treatment of choice when the diseaseis diffuse, there are no obvious metastases, and the procedure necessary to totally remove the involved area would be unusually mutilating.