To address the activation status of neddylation pathway in ICC, the expression of E1 (NAE1 and UBA3 subunits) and E2 (UBC12) enzymes as well as global NEDD8 conjugation were determined by immunohistochemical staining in tumor samples from a consecutive cohort of 322 ICC patients. Here, NEDD8 is linked to intrahepatic cholangiocarcinoma.