This paper proposes a national initiative for Medicare patients with cancer. It would include (1) a rapid-learning system for comparative effectiveness; (2) a quality measurement system; and (3) payment reforms to reward high-quality care. In implementing this strategy, the U.S. Department of Health and Human Services (HHS) would make extensive use of new computerized databases for clinical research and quality measurement. Legislation will be needed for full national implementation. Similar initiatives could be started for other priority areas in Medicare. Medicare could become a national leader in advancing high-quality, effective care.