Malignancy of the extrahepatic biliary tract is a difficult and crucial diagnosis, both clinically and pathologically. Cytologic evaluation of brushings obtained endoscopically from the biliary tree is currently the standard of care in most institutions. However, bile duct brushing cytology has been plagued by low sensitivity and interpretative difficulties in differentiating reactive from malignant cytology. This review outlines both the difficulties presented by cytomorphology and the potential of new diagnostic techniques that promise to increase sensitivity without sacrificing the high specificity of cytomorphology. Diagn. Cytopathol. 2012;40:536–541 © 2012 Wiley Periodicals, Inc.