OBJECTIVES: The cost-effectiveness of genetic testing for Lynch Syndrome for patients newly diagnosed with colorectal cancer in the UK has not previously been estimated.  Therefore, the cost-effectiveness of nine testing strategies were simultaneously compared using a detailed and rigorous mathematical model. METHODS: In the base case analysis, probands were tested only if aged 50 or below. Testing strategies included use of family history, tumour-based tests and genetic testing. The clinical pathways of thousands of individual patients diagnosed with colorectal cancer (CRC) and their relatives were simulated.  For each person, the total costs and quality-adjusted life years (QALYs) were calculated using methodology recommended by the National Institute of Health and Care Excellence (NICE). Simulated clinical events included incidence of CRC and endometrial cancer (EC); surgery for CRC and EC, colonoscopies (including bleeding and perforation), mortality from CRC, EC, colonoscopy and background causes. A proportion of people diagnosed with Lynch Syndrome were assumed to receive prophylactic hysterectomy and to undergo biennial colonoscopies (assumed to reduce the incidence and stage of colorectal cancer). The costs of treating patients with CRC with surgery, chemotherapy, radiotherapy, stoma care and palliative care were captured.  Similarly, the costs of treating patients with EC with chemotherapy and radiotherapy were included. RESULTS: The life expectancies of probands and relatives with Lynch Syndrome are estimated to increase by up to 1.6 years, depending on the strategy for genetic testing. All testing strategies are predicted to offer good value for money versus no testing, with all incremental cost-effectiveness ratios below the UK basic cost-effectiveness threshold of £20,000 per QALY.  Universal genetic testing is predicted to offer poor value for money versus targeted genetic testing. CONCLUSIONS: Results suggest that targeted genetic testing for Lynch Syndrome for patients with newly diagnosed CRC in the UK is a good use of limited financial resources.