Lung cancer remains the leading cause of cancer death among men and women in the United States. Early detection of premalignant lesions provides the possibility of treatment at earlier stages. Because malignancy develops from genetic alterations, the early detection of these genetic changes should be associated with the earliest clues to transformation. This article presents an overview of detection of molecular markers and their relevance to lung cancer. In the future, such molecular markers may play a role in guiding therapy for lung cancer.