Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that may develop at any point of the biliary tree. Their incidence is rising worldwide, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent nature of these tumours combined with their high aggressiveness and refractory nature contribute to their alarming mortality rates, representing nowadays ~2% of all cancer-related deaths yearly. In the past decade, increasing efforts have been made in order to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to increase patient's welfare.