A 33-year-old woman presented with rare brain metastases from undifferentiated high-grade sarcoma manifesting as headache and vomiting. Magnetic resonance (MR) imaging demonstrated multiple tumors in the brain, subcutaneous soft tissue, and mediastinum. The patient underwent surgery, followed by chemotherapy and radiotherapy. The histological diagnosis was undifferentiated high-grade sarcoma. Radiotherapy was effective, but the brain tumors recurred 6 months later. The patient underwent high-dose methotrexate therapy, but showed no response. Promoter hypermethylation in the O(6)-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) genes was detected and MGMT protein expression was negative in the recurrent tumor, so temozolomide (TMZ) salvage chemotherapy was given, and follow-up MR imaging showed tumor reduction. This case suggests that TMZ may be effective for brain metastasis of undifferentiated sarcoma without MGMT protein expression.