En-bloc resection is desirable for accurate histopathological assessment of tissue specimens obtained using endoscopic mucosal resection (EMR). A new EMR method using sodium hyaluronate and a small-caliber-tip transparent hood has been developed. This is a peeling-off method using a needle-knife for mucosal and submucosal incisions. Long-lasting submucosal thickening resulting from an injection of sodium hyaluronate, and good visualization of the submucosal tissue with the aid of a small-caliber-tip transparent hood, make the cutting procedures easy and safe. A large superficial gastric cancer and a large villous tumor of the sigmoid colon were endoscopically resected using this method. En-bloc endoscopic resection was successful in both patients. The gastric lesion was an well-differentiated intramucosal adenocarcinoma, completely resected in a specimen measuring 97 x 50 mm. The colonic lesion was an intramucosal well-differentiated adenocarcinoma in adenoma, completely resected in a specimen measuring 70 x 55 mm in diameter. No significant complications were noted in either patient. The new method of EMR using sodium hyaluronate and the small-caliber-tip transparent hood is a promising method for endoscopic en-bloc resection of large superficial neoplastic lesions, both in the stomach and the colon.