The prevalence of malignant peripheral nerve sheath tumor (MPNST) among the general population is only 0.001%. Most cases originate in peripheral nerve root trunks in the extremities; MPNST rarely occurs in the head and neck. We describe the case of a 61-year-old man who presented with Horner syndrome, dysphonia, and enlarged neck nodes. Imaging detected a paraspinal mass of the deep superior cervical chain next to the internal carotid artery. The patient underwent an upfront modified radical neck dissection of the right-sided lymph nodes from levels II through V. Postoperative irradiation was performed. Two years after the initial diagnosis, the patient was found to have a pulmonary metastasis of the MPNST. A wedge resection was performed, and at 6 months of follow-up, the patient was alive without disease. However, he subsequently developed soft-tissue metastases in his buttocks, and he died 2 years later of brain metastases. In our case, the clinical symptoms suggested the anatomic location of the primary tumor, and imaging findings suggested the diagnosis, which was confirmed on histopathology. As far as we know, no case of MPNST of the superior ganglia of the sympathetic chain has been previously described in the literature.