A 68-year-old woman presented with abdominal pain and melena. Urgent OGD revealed an ulcerated pedunculated subepithelial duodenal lesion, and CT/EUS confirmed a 50-mm lipoma causing intussusception. Endoscopic treatment was performed by placing an endoloop at its base and resecting most of the lesion with a 20-mm snare. Both steps were performed underwater, which provided better lesion positioning and safety, given its proximity to the duodenal walls. Histology confirmed a benign lipoma. Different strategies have been described to be safe and effective for the endoscopic treatment of gastrointestinal lipomas, including loop-and-let-go, but spontaneous detachment posed a high obstruction risk in this case. Combining loop placement with underwater resection allowed for a safe, single-session treatment also allowing histological analysis.