In the past decade, detection of micrometastatic disease in different clinical samples including pleural lavage, lymph node, bone marrow, and blood has become a rapidly growing area of interest in research of non-small cell lung cancer and esophageal cancer. The results of these studies support the concept that, just as in many other solid malignancies, systemic spread may happen at an early stage in non-small cell lung cancer and esophageal cancer. Such systemic spread is often occult (micrometastases) at the time of primary diagnosis, which may have adverse effects on survival. Improved staging can be expected with information on micrometastases, and a subgroup of patients who will benefit most from adjuvant therapy might be identified. Although reliable and standard methods need to be developed before detection of micrometastasis is incorporated in the routine clinical practice, we suggest that it be considered an important correlate in clinical trials in non-small cell lung cancer and esophageal cancer.