We report one case of leiomyosarcoma (LMS) of the larynx occurring in a patient with a history of immunosuppressive therapy, and offer a critical review of the literature. Epstein-Barr virus (EBV) genome was not identified in the neoplastic cells. The patient was treated with endoscopic resection and post-operative radiotherapy. Lung metastasis and thyroid infiltration became evident 14 months following treatment despite the absence of laryngeal recurrence. Progressive decline occurred and the patient died 15 months after diagnosis.