A 61-year-old male who complained of right upper quadrant pain was referred to the authors for evaluation
after his computed tomography suggested biliary adenocarcinoma. The lesion consisted of multiple
cysts with papillary mass and peri-ampullay mass. The patient underwent an operation due to a clinical
suspicion of biliary cystadenocarcinoma, but the pathology confirmed biliary papillomatosis (BP) after diagnosing
intrahepatic papillary neoplasm with high-grade dysplasia and invasive adenocarcinoma with papillary
neoplasm from the distal common bile duct to the duodenum. BP is a disease characterized by multiple
papillary masses. Its cause has yet to be discovered. It commonly manifests as bile duct dilation but rarely
as a ductal cystic change. Under computed tomography or magnetic resonance imaging, both the BP and
the cystic neoplasm can show bile duct dilation and a papillary mass, which makes their differential diagnosis
difficult. A confirmative diagnosis can be made through a pathologic examination. BP is classified
as a benign disease that can become malignant and may recur, though rarely. Its treatment of choice is
surgical resection. Laser ablation or photodynamic therapy can be used for unresectable lesions. In the
case featured in this paper, biliary papillomatosis was difficult to differentiate from cystic adenocarcinoma
due to diffusely scattered multiple large cystic lesions in the liver, and it was histologically confirmed to
have become malignant with cystic duct dilation after the operation. This case is reported herein with a
literature review.