Primary sclerosing cholangitis (PSC) is a progressive liver disease seen predominantly in patients who also have inflammatory bowel disease. Patients with PSC and IBD have a predisposition to developing cancer, particularly in the colon and biliary tree. There are no available treatments for PSC; however, the efficacy of simtuzumab and obeticholic acid are being investigated. This article presents evidence and guidelines for screening and early detection of colorectal carcinoma, cholangiocarcinoma and gallbladder cancer, as well as other malignancies, including hepatocellular carcinoma and pancreatic cancer. Nurses have an important role in remaining vigilant for signs of cancer and helping patients make more informed decisions.