At present, systemic treatment is not generally recommended for advanced biliary tract and gall bladder carcinomas. In particular cases, however, it may be justified to consider systemic chemotherapy treatment. In four cases we investigated the efficacy of palliative systemic treatment in metastatic biliary tract and gall bladder adenocarcinomas. Similar to the proceedings in a phase II study for metastatic pancreas adenocarcinomas, four patients with advanced biliary tract and gall bladder adenocarcinomas received a combination treatment of gemcitabine (GEM) and weekly high-dose 5-fluorouracil (5-FU) as a 24-h infusion. Altogether, the four patients received 96 chemotherapy applications. The palliative chemotherapy was tolerated well. In one patient, leukocytopenia (toxicity grade III) and thrombocytopenia (toxicity grade III) occurred. In three patients, the palliative systemic treatment led to stable disease, partly with a significant decrease of the CA 19-9 tumor marker, and in one patient to partial remission (PR). The survival times in these four patients were 6, 10, 17 and 26 months. Even in the case of PR, a curative hemihepatectomy right could be achieved after ‘downsizing’. We conclude that in the four case studies, the applied palliative combination treatment based on GEM and 5-FU proved to be effective. However, future multicenter studies will be necessary to determine the significance of palliative chemotherapy in biliary tract and gall bladder carcinomas.