Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized entity representing a spectrum of benign and malignant neoplasms of the pancreas. Preoperative distinction between benign and malignant IPMNs remains difficult. Reported predictive factors for malignancy are size of the main pancreatic duct, cystic neoplasm, and mural nodule. We report herein the case of a 50-year-old woman in whom a large mural nodule (30 mm) in the dilated main pancreatic duct (16 mm in diameter) was detected by ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography. Because the large mural nodule and dilatation of the main pancreatic duct were also detected by endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS), the main-duct IPMN was considered to have malignant potential. Thus, pylorus-preserving pancreaticoduodenectomy with lymph node dissection was performed. The resected intraductal tumor appeared polypoid with a broad stalk and comprised a proliferation of mucin-containing columnar epithelial cells with papillary structures without malignant features. The final diagnosis was intraductal papillary mucinous adenoma of the pancreas. The size of the mural nodule and the final diagnosis in this case suggest that the introduction of a novel molecular-biological approach might be necessary for the precise preoperative diagnosis of main-duct IPMN and adequate surgical treatment.