Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of the biliary tract with growing incidence and dismal prognosis. It is responsible for 10-20% of primary liver cancer worldwide, but early diagnosis is still a challenge and few treatment options are available. Aim of this review is to summarize the current knowledge about biological features and arising molecular patterns of this disease. The identification of emerging biomarkers and early detection of precursor lesions shall play a key role in the perspective of future tailored targeted therapies.