OBJECTIVES: Colorectal cancer (CRC) is one of the most common forms of cancer in western countries and represents the second leading cause of cancer mortality in Europe (AIRTUM, 2009). Early detection and removal of cancerous lesions can reduce the incidence of CRC, its mortality and improve patients’ quality of life (Taupin et al. 2006). The main literature on this topic refers to USA and few studies have been conducted in Italy to date (Zappa et al. 1997; Tappenden et al. 2007). Aim of the paper is to shed some light on the effectiveness and costs of screening programs in the Italian health care system, presenting the results of a cost-effectiveness analysis of a CRC screening program in Italy. METHODS: We use as case-study a Regional CRC screening program to determine the full costs and the effectiveness of the adopted techniques, FOBT combined with colonoscopy.The costs involved in each phase of the program are evaluated using a micro-costing analysis. Effectiveness is valued in terms of early detected lesions and years of life gained. Cost and effectiveness data are used to estimate the costs for year of life gained, using a MISCAN-COLON Model© to simulate and compare two alternative scenarios, with or without the screening program. RESULTS: The preliminary results show that the screening will prevent almost 2.0 deaths (11.2%) per 1000 screened individuals, corresponding to 19.4 years of life gained in 30 years with an incremental cost effectiveness ratio of € 2400 for life year gained. CONCLUSIONS: The results outpace those of previous studies (Sonnenberg, 2000), signalling an increasing effectiveness of CRC screening programme. Besides, the paper highlights the importance of implementing a screening not only for the effects that prevention can have in clinical terms, but also for the economic impact of such a policy in relation to the long-term sustainability of healthcare systems.