BACKGROUND:?Only 105 cases of neuroendocrine tumor (NET) of the ampulla of Vater have been described, mostly as single case reports. The incidence of NET is rising. The changes in incidence may result from changes in detection. This study was to determine the relative incidence and clinicopathological characteristics of high-grade neuroendocrine carcinoma (small cell carcinoma and large cell carcinoma) of the ampulla of Vater at a single institution. METHODS:?Sections from parafifn blocks of tumors of the ampulla of Vater taken from 45 patients who underwent Whipple's procedure and 6 patients who underwent palliative bypass between September 2003 and January 2007 were subjected to immunohistochemical analysis. The clinical and pathological data from 5 patients diagnosed with NET of the ampulla of Vater were analyzed. RESULTS:?The patients were 3 men and 2 women, ranging in age from 39 to 47 years (mean 44 years). Operative procedures included Whipple's procedure in 4 patients and palliative bypass in 1 patient. Histopathological examination revealed large-cell neuroendocrine carcinoma in 2 patients, small cell carcinoma in 2, and carcinoid in 1. Three patients with high-grade neuroendocrine carcinoma who had undergone Whipple's procedure died at postoperatively 7, 11, and 13 months. The patient who had undergone palliative triple bypass died 3 months after surgery. CONCLUSIONS:?The relative incidence of high-grade neuroendocrine carcinomas of the ampulla of Vater is higher than that generally expected. The tumors behave aggressively and have a dismal prognosis despite aggressive treatment.