Lung cancer has the highest cancer-related mortality worldwide and in the United States. Reduced tobacco consumption and advancement in therapies have led to a modest decline in lung cancer death rates over the past two decades; the overall survival rate is still disappointing. Moreover, race-associated disparities are also observed, especially in the clinical outcomes. While differences in socioeconomic status and lifestyle could be significant contributing factors, differences in the genetic landscape of lung cancer among different racial groups have also been reported. In this review, we shed light on the genetic heterogeneity of lung cancer and race-associated differences in genetic alterations to build a framework for future studies to understand the biological basis of lung cancer disparities.