A large number of patients are diagnosed every year with non small-cell lung cancer, and their prognosis and response to treatment are inversely correlated to tumor stage at initial diagnosis. Despite the surgical removal of all apparent malignancy from patients with early disease, many will relapse, presumably as a result of disease that was undetected at initial evaluation. In an effort to identify those patients who have early lymph node involvement by metastatic disease, several groups of investigators have searched for the presence of micrometastases in hematoxylin-eosin-negative lymph nodes using immunohistochemical or molecular methods. Four of six groups of investigators using immunohistochemistry have found a significant incidence of lymph node micrometastases and a direct correlation between the absence of micrometastases and disease-free survival; these are encouraging results that require confirmatory studies. Molecular methods may potentially offer increased sensitivity; however, their high cost and the requirement to process large numbers of samples limits their use to research settings at present.