Cancer in Maryland is a serious health concern for minority and underserved populations in rural and urban areas. This report describes the National Cancer Institute (NCI) supported Maryland Special Populations Cancer Network (MSPN), a community–academic partnership. The MSPN's priority populations include African Americans, Native Americans, and other medically underserved residents of rural and urban areas. The MSPN has established a community infrastructure through formal collaborations with several community partners located in Baltimore City, the rural Eastern Shore, and Southern and Western Maryland, and among the Piscataway Conoy Tribe and the other 27 Native American Tribes in Maryland. Key partners also include the University of Maryland Eastern Shore and the University of Maryland Statewide Health Network. The MSPN has implemented innovative and successful programs in cancer health disparities research, outreach, and training; clinical trials education, health disparities policy, and resource leveraging. The MSPN addresses the goal of the NCI and the Department of Health and Human Services (DHHS) to reduce and eventually eliminate cancer health disparities. Community–academic partnerships are the foundation of this successful network.