Radiation-induced leiomyosarcoma is a very rare complication following irradiation of primary malignancies. In the chest wall, it is usually secondary to radiotherapy for breast cancer or lymphoma. Esophageal malignancy is a radiation dose-related complication of radiotherapy for breast cancer, but its absolute risk is low. A 61-year-old woman presented with an esophageal leiomyosarcoma 13 years after surgery plus mediastinal irradiation (55 Gy) for a stage III thymoma. Esophageal sarcoma is an uncommon tumor, reported sporadically in the literature. Radiotherapy is frequently used in the treatment of carcinoma of the esophagus, and the increased risk of development of sarcoma arising in irradiated fields is well known. The increasing use of radiotherapy for thymoma suggests that radiation-associated malignancies of the esophagus may be seen more frequently in the future. To the best of our knowledge, this is the first report of radiation-induced esophageal leiomyosarcoma after mediastinal irradiation of a thymoma.