Therapeutic strategies for villous adenoma of the papilla of Vater remain controversial. This study evaluates the accuracy of preoperative histopathologic diagnosis and the impact of the grade of dysplasia on recurrence as well as on potential alteration of the surgical approach. A series of 32 patients with an adenoma of Vater's papilla who underwent local resection or pylorus-preserving pancreaticoduodenectomy between January 1990 and August 2000 were reviewed retrospectively. Multiple endoscopic biopsies had been performed preoperatively. The histopathology of the preoperatively obtained biopsy specimens and subsequent surgical specimens were evaluated for grade of dysplasia by two pathologists and correlated with the clinical course after operative treatment. Altogether, 3 of 11 patients (27%) with a low-grade (LG) dysplasia adenoma and 6 of 21 patients (29%) with a high-grade (HG) dysplasia adenoma in the initial endoscopic biopsy specimens exhibited invasive carcinoma at the postoperative histologic examination (NS). Recurrence was not observed in the 6 patients from the LG dysplasia adenoma group following local resection and benign postoperative histology. In contrast, recurrence of villous adenoma was discovered in 2 of 12 patients (17%) and development of invasive carcinoma in 5 of 12 patients (42%) from the preoperative HG dysplasia group (p <0.05). The overall risk of carcinoma after primary diagnosis of an HG dysplasia adenoma was 44% (14/32). Adenoma of the papilla of Vater including HG dysplasia appears to be associated with a high risk of exhibiting invasive carcinoma postoperatively and a high rate of recurrence. Therefore pylorus-preserving pancreaticoduodenectomy should be offered to patients with an HG dysplasia adenoma.