BACKGROUND Myxofibrosarcoma involving the spine is a rare and intractable disease. Although wide surgical resection is the mainstay of treatment, it is often difficult to complete marginal en-bloc resection due to adjacent neurovascular components in the spine. Separation surgery, a partial resection to achieve circumferential separation and high-dose irradiation such as postoperative intensity-modulated radiation therapy, has received much attention as a new therapy for spinal tumors. However, little evidence regarding separation surgery with intensity-modulated radiation therapy for a spinal myxofibrosarcoma exists. CASE REPORT We present a case of a 75-year-old man with progressive myelopathy. Radiological examination revealed severe spinal cord compression due to an unknown widespread multiple tumor in the cervical and thoracic spine. Computed tomography-guided biopsy showed high-grade sarcoma. Positron emission tomography detected no other tumors in the body. Separation surgery was therefore performed with posterior stabilization. Hematoxylin and eosin staining showed storiform cellular infiltrates and pleomorphic cell nuclei. Histopathology identified high-grade myxofibrosarcoma. Postoperative intensity-modulated radiation therapy of 60 Gy in 25 fractions was completed without any adverse effects. The patient had greatly improved neurological function, was capable of walking with a cane, and had no recurrence for at least 1 year after surgery. CONCLUSIONS We reported a case of an unresectable high-grade myxofibrosarcoma of the spine successfully treated with the combination of separation surgery and postoperative intensity-modulated radiation therapy. This combination therapy is a relatively safe and effective treatment option in patients with impending neurological damage by unresectable sarcomas when total en-bloc resection is challenging due to the size, location, or adhesion.