 KRAS is a downstream molecule in the EGFR-pathway. Recently it has been shown that oncogenic RAS mutations are predictive for poor efficacy of an anti-EGFR-therapy in colorectal cancer. Conversely patients with colorectal cancers harbouring KRAS wild-type showed frequently dramatic tumor responses upon anti-EGFR-treatment, indicating that colorectal cancers with KRAS wild type are highly susceptible for an anti-EGFR-therapy. Although dysregulation of KRAS is commonly observed in malignancies, mutations of KRAS have only been described in 12 to 54 of intrahepatic CCA Kubicka et al. 2001a; Blechacz and Gores 2008, Gruenberger et al 2009. This is in sharp contrast to pancreatic ductal carcinoma where KRAS mutations are present in approximately 90 of cancers. Thus, despite shared developmental ontology between the pancreatic ducts and the biliary tree, their adult cancers are different and may explain the negative result of a phase III studies in pancreatic cancer with Cetuximab anti-EGFR-antibody. 