Delayed diagnosis of colon cancer due to missed screening or follow-up leads to preventable morbidity and mortality. In this quality improvement effort, the study team sought to enhance colon cancer screening in primary care. They identified several important drivers of successful screening programs, including leadership support, patient engagement, teamwork, tracking of results, closed loops for referrals, and health information technology tools to support best practices. Sequential plan-do-study-act cycles were implemented to improve processes. Participating practices had widely varying baseline screening rates, and some sites demonstrated significant improvements from baseline while others did not change. The effort required to augment colon cancer screening in primary care demonstrates the challenge of implementing evidence-based practices in order to achieve timely diagnosis of cancer.