There is no consensus on the appropriateness of local resection for ampullary tumors, because malignant recurrence of what were thought to be benign tumors has been reported. This study examined the role of local resection in the management of ampullary tumors. Thirty patients (mean age 66 years) had transduodenal local resections performed at UCSF-Moffitt Hospital or the San Francisco VA Medical Center (February, 1992 to March, 2004). Mean follow-up time was 5.8 years. Preoperative biopsies (obtained in all patients) showed 18 adenomas, four adenomas with dysplasia, five adenomas with atypia, one adenoma with dysplasia and focal adenocarcinoma, and two tumors seen on endoscopy, whose biopsies showed only duodenal mucosa. In comparison with the final pathology findings, the results of frozen section examinations for malignancy in 20 patients, during the operation, were false-negative in three cases. The final pathologic diagnosis was 23 villous adenomas, six adenocarcinomas, and one paraganglioma. On preoperative biopsies, all patients who had high-grade dysplasia and one of five patients with atypia turned out to have invasive adenocarcinoma when the entire specimen was examined postoperatively. Two (33%) adenocarcinomas recurred at a mean of 4 years; both had negative margins at the initial resection. Among the 23 adenomas, three (13%) recurred (all as adenomas) at a mean of 3.2 years; in only one of these cases was the margin positive at the time of resection. Tumor size did not influence recurrence rate. Ampullary tumors with high-grade dysplasia on preoperative biopsy should be treated by pancreaticoduodenectomy because they usually harbor malignancy. Recurrence is too common and unpredictable after local resection of malignant lesions for this to be considered an acceptable alternative to pancreaticoduodenectomy. Ampullary adenomas can be resected locally with good results, but the recurrence rate was 13%, so endoscopic surveillance is indicated postoperatively. Frozen sections were obtained during the operation, but they were less reliable than expected. No adenomas recurred as carcinomas, suggesting that local resection is appropriate for these tumors in the absence of dysplasia or atypia on preoperative biopsies.