Background: Successful endoscopic treatment of conventional papillary adenomas is well described. However, many authors recommend surgical resection for larger lesions with extrapapillary extension. Objective: To describe the classification, technique, and outcome for the endoscopic resection of giant laterally spreading tumors of the papilla (LST-P). Design: Single-center case series. Settings: Tertiary referral academic gastroenterology unit. Patients: Patients referred for endoscopic treatment of LST-P. Intervention: Pre-resection staging and single-session endoscopic removal of papillary adenomas. For those classified as LST-P (>30 mm, extending beyond the papilla onto the duodenal wall and involving as much as two thirds of the duodenal circumference), a standardized single-session EMR technique was used. Main Outcome Measurements: Technical success, complications, and adenoma recurrence for single-session removal of LST-P. Outcomes were compared with those of conventional ampullary adenoma resection during the same period. Results: Twenty-five patients with ampullary adenomas were referred. In 10 patients identified with LST-P (mean age 70.2 years; adenoma size 30-80 mm), combination EMR and papillectomy was performed in a single session. The median admission duration was 1 night (range 0-35). Complications included bleeding (30%) and cholecystitis (10%), with no cases of pancreatitis or perforation. Adenoma recurrence at 3 months was found in 1 patient (10%). Complication and recurrence rates in smaller (<30 mm) ampullary adenoma resections were not significantly different. Limitations: A relatively uncommon entity and thus small sample size. Conclusions: Endoscopic resection of carefully staged LST-P is a viable therapeutic alternative to surgery. In experienced hands, the outcomes are comparable to those for conventional ampullary adenomas.