A wide variety of neoplastic lesions may involve the ampulla of Vater, but squamous cell carcinoma has not been reported. Here we report a case of squamous cell carcinoma of papilla Vater. A 72-year-old Chinese female was manifested by obstructive jaundice and biliary tract infection. Duodenoscopic study revealed a polypoid mass with deep and broad ulcer on the ampulla of Vater. Histological examination revealed a metastatic squamous cell carcinoma. The gynecologist had examined the patient carefully and revealed a negative tumor survey. Other sources were also intensively studied but which revealed nothing. The patient developed biliary tree infection after endoscopic retrograde cholangiopancreatic study so that percutaneous transhepatic cholangiography & drainage was performed. Pseudomonas aeruginosa and Enterococcus were cultured from the drainaged bile. Radiotherapy was used and the bleeding was halted temporarily but the patient later expired due to persistent bleeding.