Objective:To investigate the consistency between the iodine-unstained area and the pathological size of endoscopic submucosal dissection (ESD) specimens of superficial esophageal cancer.Methods:A retrospective study was performed on data of 32 patients with superficial esophageal cancer who accepted ESD from May 2019 to April 2020 in the First Affiliated Hospital, Zhejiang University School of Medicine. The maximum transverse diameter and maximum longitudinal diameter of the iodine-unstained area were compared with the tumor pathological area. A size difference no more than 0.5 cm was considered as conformity, any difference between 0.5 and 1.0 cm was considered as non-conformity, and any difference no less than 1.0 cm was considered as serious non-conformity. At the same time, pink sign after spraying Lugo solution and the consistency of pink sign area with the iodine free area were observed.Results:A total of 32 patients with 33 lesions were enrolled in this study, including 23 males and 9 females and the age of the patients was 59.5±7.3 years. There were 19 (57.6%) lesions whose size of iodine-unstained area was consistent with the tumor pathological area. These 19 lesions were all positive for the pink sign, and the pink sign area overlapped with the iodine-unstained area. In addition, 4 (12.1%) iodine-unstained areas of the lesions did not match the size of the pathological area, and 10 (30.3%) iodine-unstained areas of the lesions were seriously inconsistent with the size of the pathological area. These 14 (42.4%) lesions were all positive for pink sign, and the pink sign area was significantly smaller than the iodine-unstained area. Among the 14 discordant lesions, 2 lesions underwent ESD according to the iodine-unstained area, which resulted in excessive resection and postoperative stenosis.Conclusion:Determining the extent of superficial esophageal cancer by iodine-unstained areas before ESD may lead to excessive resection of the lesions, which is related to the fact that the iodine-unstained areas of the lesions are sometimes significantly larger than the pink sign areas. Therefore, in order to achieve precise treatment, endoscopists can choose the iodine-unstained area with positive pink sign as the first choice for resection.