Abstract. Endoscopic submucosal dissection (ESD) for upper gastrointestinal (GI) subepithelial tumors (SETs) originating in the muscularis propria (MP) layer is associated with numerous issues regarding secure closure and measures against accidental perforation. However, symptomatic benign GI SETs or carcinoid tumors originating in the submucosa (SM) may be safely resected en-bloc using ESD. In this study, the feasibility and safety of ESD as a novel method for endoscopic resection for such GI SETs revealed on endoscopic ultrasonography (EUS) was investigated. A total of 12 consecutive cases of patients with symptomatic benign SETs (n=3; 1 esophageal hemangioma and 2 gastric lipomas) or small carcinoid tumors (n=9; <10 mm, with an extremely low risk of metastasis) originating in the SM as determined on EUS, between March, 2009 and April, 2013, were retrospectively reviewed. The lesions were resected by ESD after confirming that the tumors originated from the SM. The complication rate following en-bloc resection was also determined. En-bloc resection was achieved in all 12 cases, the mean procedure time was 45 min (range, 20-120 min) and no complications occurred intra-or postoperatively. There was no tumor recurrence or disease-related mortality reported during the follow-up period (median follow-up time, 13.4 months). Histopathological curative resection was achieved with ESD without complications in all 9 cases with carcinoid tumors. Therefore, if EUS reveals a SET originating in the SM without infiltration of the MP and resection is indicated due to the presence of abdominal symptoms, ESD may be a feasible option for diagnostic treatment with minimal invasiveness. However, larger-scale prospective studies are required to establish the feasibility and safety of this procedure.