Colorectal cancer poses a serious threat to the health and well-being of individuals, especially those at high risk or over the age of 50. Gone undetected, colorectal cancer is often fatal, however, preventive screening greatly reduces the number of people who may develop this disease. The Centers for Disease Control and Prevention developed the Colorectal Cancer Screening Demonstration Program in 2005 to assess the feasibility of a national colorectal cancer screening program serving low-income and un- or underinsured populations. Qualitative case study data from the Colorectal Cancer Screening Demonstration Program evaluation were analyzed in order to examine the start-up experiences of two of the programs involved. Results from this multiple case study document program models and describe facilitators, challenges, and participant perception of the expected impact on screening behavior. Further research on program implementation is needed to understand how program models perform and impact behavior once screening begins.