OBJECTIVES: Most models developed for colorectal cancer (CRC) screening evaluations are based on the adenoma-carcinoma pathway only. Currently, there is increasing evidence that serrated lesions can also develop into CRC. This study aimed to develop a model that reflects both the adenoma-carcinoma pathway and the serrated pathway to CRC and that includes characteristics of polyps. METHODS: The Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model was built using the scientific literature, expert opinion, data from the Dutch COCOS trial and Dutch cancer registry data. A flexible model structure was chosen to examine the impact of two alternative natural history assumptions: (i) all CRCs arise from adenomas and (ii) 15% of CRCs arise from serrated lesions. The two model versions were calibrated manually using a systematic, step-by-step approach.  RESULTS: Calibration resulted in 19 parameter sets for the adenoma-carcinoma pathway and 13 for the serrated pathway, matching the age- and sex-specific adenoma and serrated lesion prevalence in the COCOS trial and several other intermediate model outcomes. For the first natural history assumption, progression rates from advanced adenoma to CRC between 1.6% and 2.7% were found to produce model-based age-standardized incidence rates within the 95% confidence interval of the Dutch incidence in 2009. For the second assumption, these progression rates were between 1.3% and 2.2%. Mean duration from adenoma to CRC was 24 years. CONCLUSIONS: The ASCCA model will be used to evaluate the (cost-)effectiveness of different screening and surveillance strategies for CRC. Future analyses will evaluate the upcoming Dutch screening program using the two calibrated model versions. The implication of different test accuracies for different types of polyps with their characteristics can be taken into account in a straightforward manner. Furthermore, the impact of structural as well as parametric assumptions concerning the serrated pathway can be addressed.