Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. It is the second most common primary liver tumor type and accounts for around 3% of all gastrointestinal cancers. CCA is very deadly disease due to its aggressiveness, late diagnosis and treatment refractory nature. The incidence and mortality rates are increasing worldwide and the therapeutic options are limited. Radiotherapy, chemotherapy (palliative), surgical resection (available for 10-30% of cases) and/or liver transplantation are options only for few patients who meet certain criteria. After curative surgery more than 50% of patients recur within 12 months. Therefore, there is increasing interest in understanding the molecular mechanisms involved in the pathogenesis of this cancer type and in identifying new targets for therapy. Moreover, good specific diagnostic and pronostic markers for CCA are still needed.