Patient, provider, and systems barriers contribute to delays in cancer care, a lower quality of care, and poorer outcomes in vulnerable populations, including low-income, underinsured, and racial/ethnic minority populations. Patient navigation is emerging as an intervention to address this problem, but navigation requires a clear definition and a rigorous testing of its effectiveness. Pilot programs have provided some evidence of benefit, but have been limited by evaluation of single-site interventions and varying definitions of navigation. To overcome these limitations, a 9-site National Cancer Institute Patient Navigation Research Program (PNRP) was initiated.The PNRP is charged with designing, implementing, and evaluating a generalizable patient navigation program targeting vulnerable populations. Through a formal committee structure, the PNRP has developed a definition of patient navigation and metrics to assess the process and outcomes of patient navigation in diverse settings, compared with concurrent continuous control groups.The PNRP defines patient navigation as support and guidance offered to vulnerable persons with abnormal cancer screening or a cancer diagnosis, with the goal of overcoming barriers to timely, quality care. Primary outcomes of the PNRP are 1) time to diagnostic resolution; 2) time to initiation of cancer treatment; 3) patient satisfaction with care; and 4) cost effectiveness, for breast, cervical, colon/rectum, and/or prostate cancer.The metrics to assess the processes and outcomes of patient navigation have been developed for the NCI-sponsored PNRP. If the metrics are found to be valid and reliable, they may prove useful to other investigators.