For scholars and policymakers alike, understanding the burden of cancer on society is a critical topic for investigation. Cancer consistently ranks as the second leading cause of death in the U.S., and cancers of the prostate, breast, lung, and colorectal areas are particularly problematic. This policy brief from the Southwest Rural Health Research Center works to understand the scope of cancer mortality in rural and urban areas of the U.S. and across census regions. It finds that age-adjusted mortality rates are higher for lung, prostate, and colon cancer in rural areas than in urban areas but also that mortality rates are lower for breast and cervical cancers in rural areas than in urban areas. In addition, this brief identifies important discrepancies in cancer mortality across regions, with lower rates in the West for all analyzed cancer types except prostate cancer, and higher rates for most cancers in the rural South.