A significant number of stenosing lesions at the hepatic hilus represent benign disease rather than hilar cholangiocarcinoma. It is unclear, however, which perioperative investigations are useful for defining benign lesions in this location. A series of 49 consecutive patients who presented with obstructive jaundice due to a stenosing lesion at the hepatic hilus were investigated by documenting elevated plasma bilirubin levels, the presence of weight loss, and elevated carcinoembryonic antigen (CEA) and Ca 19-9 concentrations. Radiologic investigations included direct cholangiography, transabdominal ultrasonography, computed tomographic (CT) scans and magnetic resonance imaging (MRI). A tissue diagnosis was obtained in all patients, and the preoperative investigations were reviewed to assess their accuracy for predicting malignancy. The final tissue diagnosis was a benign lesion in 12 patients (benign idiopathic strictures 10, choledocholithiasis 2). Among the 37 patients who presented with a malignant lesion, 2 had metastatic colorectal cancer, 7 had gallbladder cancer, and 28 had hilar cholangiocarcinoma. Of the 12 patients with benign lesions, 4 (33%) had elevated tumor markers (CEA and CA 19-9), 12 (100%) had cholangiograms suspicious for malignancy, and 9 (75%) had CT and MRI features consistent with a malignant diagnosis. Thus among patients presenting with hilar strictures approximately one-fifth are due to nonmalignant causes, but the preoperative diagnosis is difficult and resection remains the most reliable way to rule out malignancy in this site.