Controlled localized radiofrequency heating and systemic isotretinoin were used serially as therapy in a hairless dog that developed multiple cutaneous squamous cell carcinomas in chronically sun-damaged skin. During the course of therapy, four superficial tumors regressed completely, both clinically and histologically. Two larger, deeper tumors showed clinical signs of regression but histologic clearing did not occur. Both treatment modalities are known to have antitumor effects independently and may exert their effects in an additive fashion. However, it is also possible that heat-induced injury to tumor cells could lead to retinoid-mediated enhancement of an immunologic response to tumor antigens or some other process that might lead to regression.