The hard work of public health officials, physicians, and disease advocacy groups to educate Americans about the importance of early detection has resulted in uptake of screening tests at levels equivalent to or higher than in countries with organized cancer screening programs. However, the societal costs of high screening rates are larger in the United States than in other countries, including higher prices for screening, more unnecessary testing, and inefficiencies in delivery, especially in small practices. Further, screening rates are not evenly distributed across population groups, and the national expenditure on clinical and community research to promote cancer screening among individuals has not been matched by research efforts that focus on policy or clinical systems to increase screening widely throughout the population. We identify opportunities for organizational change that improve access to use, improve quality, and promote cost effectiveness in cancer screening delivery.