Although the standard treatment for gastric neoplasia is still surgical resection, endoscopic resection has been accepted for some of these lesions in an early stage. Among several methods of endoscopic resection, endoscopic submucosal dissection has been developed to remove the lesions in an 'en bloc' fashion regardless of size, shape, and location. Several knives for endoscopic submucosal dissection are available and each of them has some merits and demerits. In this lecture is shown how to perform endoscopic submucosal dissection for gastrointestinal tumors using the flex-knife, a new endoscopic device specifically designed for submucosal dissection, emphasizing its special features from the author’s experience.