Between August 1981 and April 1986, 133 patients with superficial malignant tumors not previously treated with radiotherapy were entered on a Phase I/II RTOG study evaluating hyperthermia plus definitive radiotherapy. Eligible patients included those with superficial epithelial or mesenchymal tumors less than 4 cm in depth. Protocol radiotherapy specified a tumor dose of 60 Gy delivered in 1.8–2.0 Gy fractions 5 times/week with a boost of 5–10 Gy through reduced portals to residual tumor. Protocol hyperthermia, delivered twice weekly, was to start within 15 minutes following irradiation and to consist of 60 minutes of heat to a tumor temperature of 43°C. Sixteen patients were exlcuded. Of the 117 eligible patients, the treated lesions had site/histologies which were 35% head & neck/squamous, 46% breast/adenocarcinoma, and 19% other site/histologies. Lesions were 3 cm or larger for 77% of patients. Of the 41 patients with head & neck/squamous lesions, skin or subcutaneous necrosis occurred within 6 months for 2% of the patients; 12% experienced thermal blisters. Fourteen patients were followed for 6 months or more following start of treatment; none of these experienced late toxicities more severe than telangiectasis. Complete responses were observed in 51% of these patients. Of the 54 patients with breast/ adenocarcinoma lesions, skin or subcutaneous necrosis occurred within 6 months for 13% of the patients; 17% experienced thermal blisters. Thirty-seven patients were followed for 6 months or more following start of treatment; complications observed during this period included 13% with ulceration and one case of skin necrosis. Complete responses were observed in 85% of these patients. Local control was maintained at nearly this level for at least 2 years. Logistic regression analyses showed site/histology, greatest tumor diameter and average tumor temperature to be significantly related to response. Based on these promising findings, the RTOG has instituted a randomized Phase III study evaluating radiation therapy with or without hyperthermia in this patient population.