Introduction: Adenosquamous carcinoma (ASC) of the bile duct is a rare diagnosis with poorly understood clinicopathological characteristics and disease progression, so identification of the features associated with ASC patient survival is warranted. 
Materials and methods: A population cohort study was performed using prospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database for patients with histological diagnoses of ASC of the bile duct from 1973 to 2013.
Results: A total of 106 patients with ASC of the bile duct were included (mean age 68.1±13.5 years). Lesions from 58 patients were in the extrahepatic bile duct and 34 were located at the ampulla of Vater. Fifty-seven patients were categorized with a regional stage, 15 had localized disease, and 30 had distant disease. Most (60.4%) patients received cancer-directed surgery, and radiation was performed in 14.1% of cases. The 1-year, 2-year, and 5-year overall survival (OS) for patients with ASC of the bile duct was 30.1%, 11.3%, and 3.7%, respectively. Cancer-directed surgery offered 10 additional months of OS for patients with ASC of the bile duct and median OS was 14.0, 6.0, and 6.0 months for ampulla of Vater, extrahepatic bile duct, and intrahepatic bile duct cases, respectively. A multivariate Cox analysis showed that lesions in the ampulla of Vater (HR=0.51, 95% CI 0.26–0.99) and having surgery (HR=0.34, 95% CI 0.14–0.81) were independent protective prognostic factors for these patients.
Conclusion: Cancer-directed surgery and a primary lesion site of the ampulla of Vater may suggest favorable prognosis for patients with ASC of the bile duct.
Keywords: adenosquamous carcinoma, bile duct, prognosis, SEER database