Biliary tract cancer (BTC) is a rare disease with a heterogeneous nomenclature. Carcinomas of the intra- and extrahepatic biliary tract as well as gallbladder cancer are oftentimes combined in clinical research and treatment algorithms. However, these different cancer types vary not only in their anatomical features, but also in the underlying molecular alterations.Surgery remains the only chance of cure. Adjuvant chemotherapy with capecitabine for 6 months should be recommended after curative intended surgery. In the palliative first-line treatment of advanced BTC, the combination chemotherapy gemcitabine and cisplatin remains the only evidence-based standard. For second-line treatment, the combination of 5-FU, folinic acid and oxaliplatin (FOLFOX) is a treatment option based on preliminary data from a randomized phase 3 study. Potential targeted therapies showing efficacy in prospective clinical studies are, for example, IDH-, BRAF-/MEK- and FGFR-inhibitors as well as immunotherapy. Therefore, in the era of personalized medicine, molecular testing should be offered to all patients with advanced disease and indication for systemic treatment.
