We report a 62-year-old woman and a 66-year-old woman with abdominal pain and acute onset of jaundice, respectively. Preoperative cholangiopancreatography, cholangiography, and ERCP showed masses in the ampulla of Vater. Biopsy showed small cell carcinoma, and the tumor cells were immunoreactive for neuron-specific enolase, chromogranin A, and synaptophysin. Pancreatoduodenectomy or chemotherapy with radiation was performed in each patient. Histopathologic investigation disclosed direct invasion deep to the lamina propria, and infiltration of the pancreatic parenchyma, duodenum, and bile duct in the pancreatoduodenectomized patient. One patient died due to multiple liver metastases of the carcinoma of the ampulla of Vater 7 months after initiation of chemotherapy and radiotheraphy, and the other died 4 months after pancreatoduodenectomy. As in previously reported cases of small cell carcinoma of the ampulla of Vater, the present two cases showed extremely aggressive clinical course with early metastases resulting in fatal outcome.