Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disease of unknown etiology, and its occurrence with malignant tumor is extremely rare. We herein report a case of KTS presenting chronic gastrointestinal bleeding and complicating with adenosquamous cell carcinoma (ASCC) of the esophagus. The therapeutic dilemma of managing ASCC of the esophagus in a patient who combined with the rare congenital syndrome posed a difficult and interesting clinical problem. However, ASCC is also a very rare histological tumor in the esophagus, and its relationship to KTS has never been reported. In this article, we reviewed all the reported malignancies related to KTS. The possible surgical risks and complications, as well as preoperative imaging investigation, are also discussed.