Preservation of the sciatic nerve is difficult in cases of highly malignant soft tissuetumors closely surrounding the nerve. Herein, we present the first case of preservation of thisnerve by combining an in-situ preparation technique (ISP; a technique enabling the preparation ofneurovascular bundles without contamination by tumor cells) with intensive concurrent neoadjuvantchemo-radiotherapy with hyperthermia (RHC; radio-hyperthermo-chemotherapy). A 62-year-oldman presented with a soft tissue mass in the right thigh and was diagnosed with undifferentiatedpleomorphic sarcoma. The tumor arose in the multi-compartment areas of the posterior thigh musclesand was closely intertwined with the sciatic nerve. As preoperative therapy, RHC was performedfor surgical down-staging and the tumor partially responded. Afterwards, wide resection of thetumor with preservation of the sciatic nerve using ISP was performed. Following the surgery, therehas not been recurrence in the affected site and the functional outcomes of the lower extremityachieved 80% in the Musculoskeletal Tumor Society score. The patient is still alive with disease fiveyears postoperatively. This is the first case in which ISP and RHC procedures were combined forthe preservation of the neurovascular structure. Further study is needed for the validation of thefeasibility of this method.