Undifferentiated pleomorphic sarcoma (UPS), a rare soft tissue sarcoma subtype, mainly occurs in the deep parts of the limbs and trunk, observed as rapidly growing painless lumps, rarely located under the skin or protrudes from the skin surface. The risk of recurrence and metastasis is associated with multiple factors. Mutation of tumor gene, tumor occurrence, location and depth of invasion, and tumor size have great influence on prognosis. In this study, we described a case of UPS with KRAS/NF1 co-mutation. This case had undergone UPS extended resection for four times combined with chemotherapy in another hospital. The resection area was more than 3 cm, and tumor relapsed after all operations. This time, the tumor protruded from the left lateral surface with ulceration and infection. Due to multiple surgeries, the anatomy of the lateral femoral vessels has been seriously damaged. We performed expanded tumor resection and adjacent flap transfer repair; meanwhile, vacuum sealing drainage (VSD)-negative pressure closed the drainage, and the patient recovered well after surgery. After surgery, the patient was transferred to the Department of Oncology for chemotherapy. There was no recurrence after 6 months of follow-up. Gene mutation plays an important role in UPS recurrence and metastasis. At the same time, occurrence and location, depth, and size of UPS have great influence on the prognosis. Deeper exploration and expanded resection are important for the prognosis of UPS.