Several models of colorectal cancer (CRC) screening cost-effectiveness have been published. Most of them are based on US costs of parameters/tests used. OBJECTIVE: The purpose of this analysis was to provide a model to compare several screening programs using cost data related on Italian reimbursement system, both for ambulatorial and for hospital services. METHODS: Four screening programs were assessed in comparison with non screening program: annual fecal occult blood test alone (FOBT), flexible sigmoidoscopy every five years (FS), FOBT and FS combined and one-time colonscopy (CO). The analysis was carried out by considering a 10-years screening period. Effectiveness data derived from recent literature; cost-effectiveness was defined as "cost per cancer prevented" (CCP) and "cost per cancer death prevented" (CCDP). Computer analysis was performed using algebraic formula. Data robustness was tested with sensitivity analysis of main variables: patient compliance, cost of cancer care and cost of CO complication. Maximization analysis was carried out on risk population (selected screening). RESULTS: CO had the greatest impact on CRC mortality followed by FS+FOBT, FS and FOBT. CO resulted also the most cost-effective program, both for CCP and for CCDP, followed by FOBT+FS, FS and FOBT for all the compliance levels considered. Sensitivity analysis reinforced these results. Maximization analysis amplify both efficacy and cost-effectiveness of CO as test for selected screening. CONCLUSION: This model, even with the limitation linked to cost assumption problems, seems to be useful for authorities which will organize general population CRC screening programs.