BACKGROUND In 2005 through 2009, the Centers for Disease Control and Prevention (CDC) funded 5 sites to implement a colorectal cancer screening program for uninsured, low-income populations. These 5 sites composed a demonstration project intended to explore the feasibility of establishing a national colorectal cancer screening program through various service delivery models. METHODS A longitudinal, multiple case study was conducted to understand and document program implementation processes. Using metaphor as a qualitative analytic technique, evaluators identified stages of maturation across the programmatic life cycle. RESULTS Analysis rendered a working theory of program development during screening implementation. In early stages, program staff built relationships with CDC and local partners around screening readiness, faced real-world challenges putting program policies into practice, revised initial program designs, and developed new professional skills. Midterm implementation was defined by establishing program cohesiveness and expanding programmatic reach. In later stages of implementation, staff focused on sustainability and formal program closeout, which prompted reflection about personal and programmatic accomplishments. CONCLUSIONS Demonstration sites evolved through common developmental stages during screening implementation. Findings elucidate ways to target technical assistance to more efficiently move programs along their maturation trajectory. In practical terms, the time and cost associated with guiding a program to maturity may be potentially shortened to maximize return on investment for both organizations and clients receiving service benefits. Cancer 2013;119(15 suppl):2926-39. (c) 2013 American Cancer Society. In a longitudinal qualitative evaluation of 5 sites that the Centers for Disease Control and Prevention funded to provide colorectal cancer screening programs for uninsured, low-income populations, a developmental model was discovered to represent the programs' maturation over time. Demonstration sites evolved through common stages during screening implementation, suggesting key areas of technical assistance to more efficiently move programs along their maturation trajectory.