BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.