We report the case of a sixty-six year-old man admitted at our hospital with a suspected malignant tumor of the ampulla of Vater. The patient underwent a Pylorus-preserving pancreatico-duodenectomy. Histology showed a signet-ring cell carcinoma of the ampulla of Vater. This case is the 13th report in the literature of a signet-ring cell carcinoma of the ampulla of Vater.