Primary adenosquamous carcinoma of the ampulla of Vater is extremely rare. We report two cases of adenosquamous carcinoma of the ampulla of Vater in a 48-year-old female and an 80-year-old female patient. The gross appearance was a polypoid mass in both cases. Histologically, the majority of the two tumors was composed of squamous cell carcinoma with some intermingled glandular adenocarcinoma components in both cases. Squamous cell carcinomas showed an abrupt transition from the normal glandular epithelium or glandular adenocarcinoma. Although the two cases revealed duodenal wall invasion and lymph node metastasis was found in case 2, both patients are still alive at 19 and 46 months after surgery, respectively.