In Japan, the majority of esophageal cancers are squamous cell carcinomas. Because no lymph node metastasis was reported in squamous cell carcinomas limited to the intraepithelial layer (m1) or proper mucosal layer (m2), the Japanese Esophageal Association recommended endoscopic mucosal resection (EMR) as the treatment of choice for these cancers. However, these lesions often spread laterally, exceeding the limits of en bloc resectability with conventional EMR methods such as the EMR cap method. The lesions resected in piece-meal manner with conventional EMR methods are prone to recur locally. Therefore, we developed a method of mucosal resection with a hook-knife that enables endoscopic submucosal dissection safely and achieves a high rate of en bloc resection for larger lesions. The median size of the resected specimen and cancer by our method was 32 mm (range, 8-76 mm) and 28 mm (range, 4-64 mm), respectively. The en bloc resection rate was 95% (95 of 102) and the local recurrence rate was 0% (0 of 102). This procedure was safe, with only 6 cases (6%) of mediastinal emphysema, which improved with conservative treatment. Endoscopic submucosal dissection with the hook knife is a method of endoluminal surgery enabling large en bloc resections without increased surgical risks.