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Cholangiocarcinoma (CCA) is a very aggressive tumor with poor survival, the diagnosis of which is increasing. Although its cause is still unknown in most cases it is attributed to inflammatory conditions, including primary sclerosing cholangiitis, liver fluke infestation, and hepatolithiasis, but progress in molecular pathogenesis has revealed the importance of genetic alterations. The diagnosis of CCA is difficult, mainly because access to the tumor is not easy. Biopsy is possible only for intrahepatic CCA, which accounts for 10% of cases. Routine brush cytology from endoscopic retrograde cholangiography has high specificity (100%) but unfortunately it is of low sensitivity (in the range of 30%). The treatment of CCA is challenging as it is usually difficult to determine when radical surgical treatment, local resection or liver transplantation is possible, and its prognosis is still dismal. This is a review of the evolution of diagnostic techniques for CCA from routine brush cytology to modern molecular techniques, and in particular fluorescence in situ hybridization (FISH) and digital image analysis (DIA), and of its treatment. [ABSTRACT FROM AUTHOR]