Endoscopic submucosal dissection (ESD) is an useful therapeutic technique for large gastrointestinal epithelial tumors that it provides an en bloc resection. Although there is some controversy about the role of ESD for colorectal lesions, for large lesions in the distal rectum, ESD has the advantage of preserving anal function. However, the large amount of insufflating gas used during the procedure can cause severe abdominal pain and discomfort. Moreover, high intra-luminal pressure caused by a by large amount of gas can cause a micro-perforation. There is no consensus as to whether ESD is the optimal treatment for synchronous large colorectal laterally spreading tumors (LSTs) that cannot be removed en-bloc by conventional endoscopic mucosal resection. Here, a case with two neighboring synchronous large LSTs, one located in the rectum and the other in the distal sigmoid colon, were sequentially removed by separate ESD procedures performed on two consecutive days in a patient who could not tolerate a long procedure.