Lung cancer is the leading cause of cancer deaths in both men and women in the US. While most sporadic lung cancer cases are related to environmental factors such as smoking, genetic susceptibility may also play an important role and a number of lung cancer associated single-nucleotide polymorphisms (SNPs) have been identified although many remain to be found. The collective effects of genome-wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have been linked with quantitative variations of complex traits and diseases. Here we studied MAC in lung cancer using previously published SNPs data sets (US and Finland samples) and found higher MAC in cases relative to matched controls. A set of 5400 SNPs with MA (MAF < 0.5) more common in cases (P < 0.08) and linkage disequilibrium (LD) r2 = 0.3 was found to have the best predictive accuracy. These results identify higher MAC in lung cancer susceptibility and provide a meaningful genetic method to identify those at risk of lung cancer.