Most ampullary lesions (ALs) are sporadic, involve the major papilla, and are premalignant (adenomas). They are often diagnosed as an incidental finding during endoscopy or imaging procedures. Diagnosis and staging of ALs include endoscopic, histologic, and radiological evaluations. Currently, endoscopic papillectomy is the preferred treatment for ALs in most situations. In this article, we will describe the diagnostic work-up and focus on the endoscopic treatment, including indications, technique, outcomes, complications, and follow-up.