The proposed lung cancer stage classification system remains grounded in anatomic characteristics, although the large patient database contributing to this revision has dramatically expanded our body of knowledge. Predictably this has led to increased complexity due to the identification of an increasing number of subpopulations of patients. Patterns of clinical presentation characterizing these subgroups may provide clues about the propensity of tumors within a subgroup toward a particular pattern of biologic behavior. This article explores concepts regarding tumor biology that can be applied to the anatomically based new staging system.