We report a case of advanced esophageal cancer successfully treated with neoadjuvant chemoradiotherapy followed by esophagectomy in a 53-year-old man with situs inversus totalis. Upper gastrointestinal endoscopy in a clinical examination revealed a tumor in the lower third of the esophagus, and moderately differentiated squamous cell carcinoma was diagnosed from the biopsy findings. He was referred to us and the disease was diagnosed as esophageal cancer (clinical T3N1M0, cStage III) after further evaluation. According to the therapeutic strategy of our department, neoadjuvant chemoradiotherapy was commenced. The regimen was composed of radiotherapy (2 Gy/day, 5 days/week, 4weeks, total 40Gy) with cisplatin (70 mg/m2/day, day 1) and 5-FU (700 mg/m2/day, day 1-4). We performed a subtotal esophagectomy with radical lymph node dissection through a left thoracotomy because of the existence of situs inversus totalis. The thoracic operation could be performed with relatively safety because the organs were arranged in a mirror image of their normal positions. On the other hand, it was relatively difficult to construct a gastric tube. In particular, ligation of the gastrosplenic ligaments was difficult and this led to increased blood loss compared with usual operation. Histopathological examination revealed no residual carcinoma at the site of the primary focus. The patient has been followed up periodically on an outpatient basis and has remained free of recurrence for longer than 2 years 5 months after surgery.