We report the case of a 56-year-old woman who presented with biliary obstruction due to a neoplasm involving the duodenum in the area of the ampulla of Vater and the head of the pancreas. Clinically and radiographically, she was thought to have pancreatic carcinoma. Histologic examination of the specimen from a Whipple procedure revealed malignant lymphoma, follicle center type, follicular, grade 1 of 3 (follicular, predominantly small cleaved cell type), arising in the duodenum and invading the pancreas. Five peripancreatic lymph nodes were partially involved by lymphoma. Follicle center lymphoma presenting as a mass involving the ampulla of Vater with jaundice has not been described previously. Our case indicates that this type of lymphoma can occur in this location and can present with features that mimic pancreatic carcinoma.