A 61-year-old woman with an abnormal radiograph shadow in her anterior mediastinum was admitted to our hospital and underwent an extended thymectomy. The pathological diagnosis of the tumor was a non-papillary adenocarcinoma of the thymus in pathological stage IV b using the Masaoka classification owing to mediastinal lymph node metastasis. We found parasternal lymph node metastases 5 months after her first operation, and subsequently, she underwent surgery and adjuvant radiotherapy. We found systemic lymph node metastases and metastatic lesions in distant organs, including her lungs, brain, and kidney 27 months after her first operation. Systemic chemotherapy, such as carboplatin plus paclitaxel and an ADOC regimen were not very effective, so we performed immunohistochemical staining of the primary thymic adenocarcinoma. The levels of both thymidylate synthase and dihydropyrimidine dehydrogenase were low; therefore, we started S-1 100mg/body (2 weeks of administration, 1 week of withdrawal)31 months after her first operation. She entered complete remission 6 months after the initiation of S-1. We surgically resected her solitary lung metastasis 13 months after initiation of S-1, and then continued the S-1 treatment. There was no recurrence for more than 2 years after the lung surgery. We believe that when the expression levels of thymidylate synthase or dihydropyrimidine dehydrogenase are low in cases of recurrent thymic adenocarcinoma, S-1 may be able to induce an effective response.