Cancer is the second leading cause of death in the United States. Although descriptive analyses of mortality data are used often to identify variations by time and person, analyses that focus on regional variations are less common. Appalachia is a U.S. region with a high prevalence of risk factors for cancer (e.g., tobacco use, physical inactivity, and inadequate access to medical care). Analyses that focus on Appalachia provide valuable information for cancer control, research, and intervention. To assess the impact of cancer in Appalachia, researchers from the University of Kentucky and Pennsylvania State University, in collaboration with CDC, analyzed mortality data from CDC's National Center for Health Statistics for 1994-1998. This report summarizes the results of that analysis, which indicate elevated cancer mortality, underscoring the need for ongoing cancer prevention and control programs as a major public health priority in this region.