Inflammatory myofibroblastic biliary strictures (IMBS) are a rare cause of jaundice in patients with dominant strictures by ERCP and no prior biliary surgery. Because the clinical presentation of IMBS masquerades as bile duct cancer, these benign lesions are usually identified following extended hepatobiliary resection. We describe the clinical management as well as the pathologic and molecular features of IMBS in an effort to characterize this rare cause of benign biliary strictures. Methods: A consecutive series of inflammatory myofibroblastic biliary strictures (IMBS) treated between 1998-2005 was analyzed. We characterized the clinical presentation, radiographic findings, preoperative cytology, surgical management, pathologic features, and postoperative outcome of patients with IMBS. All pathologic specimens were reviewed, and additional immunohistochemistry (IHC) and loss of heterozygosity (LOH) analysis was performed. Results: Ten patients with suspected bile duct cancer were found to have IMBS on final pathology. All presented with jaundice, were evaluated by CT and ERCP, had negative cytologic brushings, and underwent surgical exploration for a dominant biliary stricture. Five patients had a preexisting autoimmune disease and a sixth developed it during follow-up. Eight patients underwent extrahepatic bile duct resection with five concomitant liver resections. Two patients underwent incisional biopsy for unresectable strictures. Light microscopy showed fibrous lesions admixed with chronic inflammation. By IHC, the lesions were negative for cytokeratin, ALK1, CD21, S100, Ki67 and p53, and focally positive for CD34. Smooth muscle actin (indicating myofibroblasts) was positive in all lesions except one (this patient died from metastatic adenocarcinoma of unknown primary). Adjunctive LOH in 2 cases revealed no K-ras mutations and one allelic loss. 6 patients received postoperative steroids. After 31 month median follow-up (4-85 months), 6 patients are alive without evidence of disease. Two patients died without recurrence, and one is lost to follow-up. Conclusions: IMBS is a rare cause of benign biliary stricture that masquerades as cholangiocarcinoma but responds to resection and steroid management. IMBS is more common in the setting of autoimmune disease and cannot be identified preoperatively with cytologic brushings. IHC indicates a myofibroblastic lesion with normal p53 expression and absent markers for cellular proliferation (Ki67) and carcinoma (cytokeratin). Evaluation by LOH analysis is an area of future interest. To our knowledge this series is the most definitive characterization of IMBS to date.