Adenoid cystic carcinoma (ACC) occurs mainly in the head and neck. Tracheal ACC (TACC) is uncommon. Primary resection is recommended as the main treatment of choice, and radiotherapy is considered for residual disease in the postoperative setting. Definitive radiotherapy is an alternative approach to cure unresectable TACC. As the status of radiosensitivity in TACC is uncertain, the evidence for radiotherapy in unresectable TACC is not well established, especially in terms of the optimal dosage and its response evaluation. Herein, we report a case of locally advanced TACC.A 49-year-old woman was diagnosed with TACC, which included a range of lesions arising in the upper trachea extending caudally 2 cm to 7 cm of the glottis. She was treated with definitive radiotherapy, given the low likelihood of complete resection of the disease. Due to the indolent growth and the propensity for infiltration along the airways, the scheduled radiation dose of 76 Gy in 38 fractions with 6-MV X-ray delivered by intensity-modulated radiotherapy was conducted to the primary tumor volume. After irradiation of 40 Gy, the patient's dyspnea on exertion was dramatically relieved and bronchoscopy revealed that the previous large polypoid intra-luminal mass was significantly eliminated, with near-complete response. The patient completed two phases of scheduled radiotherapy, and acute reactions to treatment included subjective chest tightness and grade 2 esophagitis, managed medically. After 5 years of treatment, the patient is alive without recurrent disease, and there were no serious late radiation esophagus and lung damage, with only slight dysphagia without perforation and fistula.Taken together, TACC is uncommon and the treatment of unresectable TACC is challenging. This case indicated that patients with unresectable TACC who rapidly respond to radiation may benefit from primary radical radiotherapy. Radiotherapy may be considered an effective alternative treatment modality.©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.