Persons with a history of eczema have been shown to have a reduced risk of lung cancer, but the evidence has been inconclusive because of the small size of previous studies and their limited ability to control for confounding by smoking. The objective of this study was to determine the role of eczema in relation to lung cancer while overcoming the limitations of previous investigations. Study subjects included 2,854 cases and 3,116 population and hospital controls recruited during 1998-2001 from 16 areas in the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and the United Kingdom. Odds ratios were calculated for self-reported history of eczema via multivariate logistic regression modeling. The odds ratio for a history of eczema was 0.61 (95% confidence interval: 0.48, 0.76) after control for age, sex, study center, and cumulative tobacco smoking. There was no heterogeneity in the results by sex or age at onset of eczema. Subjects reporting use of medication for eczema had a lower odds ratio than subjects not reporting such use. This study provides further evidence for an inverse association between history of eczema and lung cancer risk, which is unlikely to be due to chance, bias, or confounding.