The combination of ulcerative colitis, sclerosing cholangitis and coeliac disease is unusual. The two cases described here illustrate that the investigation and management of such patients can be difficult. Other diagnoses should be considered when a patient with a known pathology fails to respond to treatment. Review of the literature suggests an increased malignant potential in these patients. We conclude that patients with a combination of ulcerative colitis, sclerosing cholangitis and coeliac disease should undergo annual colonoscopic surveillance. In those with clinical deterioration and weight loss, early liver and bowel imaging should be carried out.