The causes of CUP are not fully understood, and there is currently no clear prevention strategy. However, general advice about ways to reduce cancer risk should be advised. Consideration should also be given to identifying individuals carrying a deleterious mutation conferring increased genetic risk. In some cases, CUP may be a manifestation of an undiagnosed hereditary cancer syndrome, with implications for the patient and their family. Patients with CUP with a significant family history of multiple cancers may suggest a heritable mutation within the family such as Lynch syndrome or a germline P53 or BRCA mutation. These patients should be referred to a familial cancer centre for further assessment.