Skull metastases can occur with nearly all types of tumor. They frequently are asymptomatic, causing local swelling, which is usually painless and rarely leads to neurological dysfunction. Carcinoma of the ampulla of Vater is an uncommon tumor accounting for approximately 0.2% of all gastrointestinal malignancies, with an estimated incidence of less than 6 cases per 1,000,000 population per year. We report about an extremely rare case of a 54-year-old female patient with a right frontal skull metastases of an ampulla of Vater adenocarcinoma 5 years after pylorus-preserving pancreaticoduodenectomy. Literature review revealed only one published case of cranial bone metastases of carcinoma of the ampulla of Vater. To the best of our knowledge this is the first case report of skull metastases of ampullary adenocarcinoma after a symptom-free interval of 5 years after R0 resection of the primary tumor, and the second published case that involves the skull.