Malignant smooth muscle tumors usually develop in the uterus and gastrointestinal tract due to the abundance of smooth muscle. They rarely develop in the soft tissue of the mediastinum. We report a 44-year-old male with neurofibromatosis type I who suffered from leiomyosarcoma extending between the left supraclavicle and the left-side middle mediastinum. The patient received debulking surgery to salvage the compromised airway and disabled upper limb. He then refused adjuvant therapy and expired 7 months postoperatively due to recurrence. To our knowledge, this type of case has never been reported in the literature.