Previous research has documented increased lung cancer incidence and mortality in Appalachia. The current study tests whether residence in coal-mining areas of Appalachia is a contributing factor. We conducted a national county-level analysis to identify contributions of smoking rates, socioeconomic variables, coal-mining intensity and other variables to age-adjusted lung cancer mortality. Results demonstrate that lung cancer mortality for the years 2000-2004 is higher in areas of heavy Appalachian coal mining after adjustments for smoking, poverty, education, age, sex, race and other covariates. Higher mortality may be the result of exposure to environmental contaminates associated with the coal-mining industry, although smoking and poverty are also contributing factors. The knowledge of the geographic areas within Appalachia where lung cancer mortality is higher can be used to target programmatic and policy interventions. The set of socioeconomic and health inequalities characteristic of coal-mining areas of Appalachia highlights the need to develop more diverse, alternative local economies.