Appalachian Kentucky (App KY) leads the nation in lung cancer incidence and mortality. Trace elements, such as As, have been associated with lung cancers in other regions of the country and we hypothesized that a population-based study would reveal higher trace element concentrations in App KY individuals with cancer compared to controls. Using toenail and drinking water trace element concentrations, this study investigated a possible association between lung cancer incidence and trace-element exposure in residents of this region. This population-based case-control study had 520 subjects, and 367 subjects provided toenail samples. Additionally, we explored the relationship between toenail and fingernail trace-element concentrations to determine if fingernails could be used as a surrogate for toenails when patients are unable to provide toenail samples. We found that, contrary to our initial hypothesis, trace element concentrations (Al, As, Cr, Mn, Co, Fe, Ni, Cu, Se, and Pb) were not higher in cancer cases than controls with the exception of Zn where concentrations were slightly higher in cases. In fact, univariate logistic regression models showed that individuals with lower concentrations of several elements (Al, Mn, Cr, and Se) were more likely to have lung cancer, although only Mn was significant in multivariate models which controlled for confounding factors. While drinking water concentrations of Al, Cr and Co were positively related to cancer incidence in univariate models, only Co remained significant in multivariate models. However, since the drinking water concentrations were extremely low and not reflected in the toenail concentrations, the significance of this finding is unclear. We also found that fingernail concentrations were not consistently predictive of toenail concentrations, indicating that fingernails should not be used as surrogates for toenails in future studies.