This report describes the experience in 40 evaluable patients entered into a Radiation Therapy Oncology Group (RTOG) study to evaluate the feasibility of administering 45°C for 15 minutes for superficial malignant lesions: 18 patients (45%) tolerated only 1 heat session at 45°C; 7 (17.5%), 2 sessions; 4 (10%), 3 sessions; and 3 (7.5%) tolerated ≥4 sessions. The overriding reason for discontinuing a 45°C treatment was pain. Of the 40 evaluable patients, 22 (55%) had complete tumor regression, and 8 (20%) had partial regression. Tumors ≤ 3 cm in diameter had significantly better complete tumor response than lesions > 3 cm (85% vs 41%) (p = .02). We conclude that 45°C heating is difficult to use in patients chiefly because of pain; this may be due in part to inadequacy of currently available external hyperthermia equipment. Caution must be exercised in the application of thermal isoeffect heat dose concepts in clinical practice until further trials have been performed and a better understanding of the time-temperature relationship is established.