Undoubtedly, K-Ras-induced lung adenocarcinoma development can proceed via multiple pathways; nonetheless, the high frequency of Runx3 inactivation in K-Ras-induced mouse and human lung adenocarcinoma suggests that a major pathway involves Runx3 inactivation before K-Ras activation. The gene discussed is RUNX3; the disease is lung adenocarcinoma.