Aim:In oncology, thermal therapy is the application of external heat to fight cancer cells. The goal ofwhole-body thermal treatment (WBTT) is to raise the patient’s core temperature to 39–42 C, and rep-resents the only thermal treatment modality that can act on both the primary tumor and distantmetastases. However, WBTT carries potential risks for toxicity when applied without accurate thermom-etry and monitoring.Methods:ElmediX has developed a medical device,HyperTherm, to deliver long-term controlled andaccurate WBTT (41.5 C, up to 8 h). The safety of the device and thermal treatment protocol was ini-tially evaluated in minipigs, and we present the confirmation of tolerability of WBTT in dogs withadvanced cancer, in combination with a reduced dose of radiotherapy or chemotherapy.Results:Thermometry in liver, rectum, and tumor confirmed a homogeneous heating of these bodyparts. Monitoring of clinical parameters showed acceptable and reversible changes in liver, cardiac,muscle and coagulation parameters, as was expected. Combination of WBTT with both radiotherapyand chemotherapy only caused some low-grade adverse events.Conclusion:We conclude that our findings support the safe use ofHyperTherm-mediated WBTT forcanine patients with advanced malignancies. They also tend to support a genuine therapeutic poten-tial for long-term WBTT which needs to be confirmed on a larger dog patient population. Combinedwith previously reported safety results in minipigs, these contribute to support the ongoing clinicalevaluation of WBTT in advanced human cancer patients.