Surgery is the main therapy for malignancies of the gastrointestinal tract. Lymph node metastasis is one of the major factors in predicting patients' clinical course and choosing appropriate adjuvant therapy after surgery. The concept of micrometastasis to regional lymph nodes emerged over 10 years ago, but its significance has been controversial. To clarify the relevance of micrometastasis of gastrointestinal tract cancers, we have established RT-PCT based-diagnostic methods using multi-markers such as CEA, CK20, and Mage 3. Prospective studies have shown that not a few micrometastasis-positive patients with carcinoma of the colon, stomach, and esophagus suffered disease recurrence, even though they did not show histologically positive lymph node metastasis. They were initially diagnosed as node-negative, and thus predicted to be disease free. A retrospective study of 62 patients with stage II node-negative colorectal cancer showed that 5-year overall survival was 78.2% among micrometastasis-positive patients, against 95.3% micrometastasis-negative patients. Moreover, there was a marked difference in 5-year disease-free survival, with 61.4% versus 88.4%, respectively. These data warrant further prospective study with a large population since RT-PCR based detection systems for micrometastasis appear to have the potential to improve conventional diagnosis and therapy for colorectal cancer.