Cancer centers, particularly those supported by the National Cancer Institute, are charged with reducing the cancer burden in their catchment area. However, methods to define both the catchment area and the cancer burden are diverse and range in complexity often based on data availability, staff resources, or confusion about what is required. This article presents a review of the current literature identifying 4 studies that have defined various aspects of the cancer burden in a defined geographical area and highlights examples of how some cancer centers and other health institutions have defined their catchment area and characterized the cancer burden within it. We then present a detailed case study of an approach applied by the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center to define its catchment area and its population cancer burden. We cite examples of how the Cancer Center research portfolio addresses the defined cancer burden. Our case study outlines a systematic approach to using publicly available data, such as cancer registry data, that are accessible by all cancer centers. By identifying gaps and formulating future research directions based on the needs of the population within the catchment area, epidemiologic studies and other types of cancer research can be directed to the population served. This review can help guide cancer centers in developing an approach to defining their own catchment area as mandated and applying research findings to this defined population.