A 55-year-old woman presented with symptomatic malignant peripheral nerve sheath tumor (MPNST) of the right hypoglossal nerve, characterized by six months of pain radiating to the right ear, headaches, and swelling over the submandibular region. Initial diagnosis was confirmed through a biopsy, and the treatment regimen included surgical resection followed by radiation therapy.

About half of MPNSTs, an uncommon kind of soft tissue sarcoma, are linked to a mutation in Neurofibromatosis type 1 (NF1), with the remaining cases being random. Because these tumors are rare and aggressive, they frequently pose difficulties for diagnosis and treatment. This case presents a unique clinical setting due to the unusual involvement of the hypoglossal nerve.

A multidisciplinary strategy is usually used in the therapy of MPNST, with surgery serving as the main treatment to establish local control. In order to lower the chance of recurrence, radiation therapy is frequently used after surgery. Depending on the patient's state and the behavior of the tumor, chemotherapy might be considered in some circumstances.

This case highlights the necessity of considering MPNST in differential diagnoses for patients with similar symptoms, particularly in those with NF1. Early detection and comprehensive treatment are essential for improving patient outcomes in such complex and rare malignancies.