Almost one third of patients with "node-negative" colorectal carcinoma (CRC) develop systemic disease. This implies that these patients have occult disease that is inadequately treated by surgery alone. We have coupled sentinel lymph node mapping and a focused pathologic examination to detect occult nodal micrometastases in CRC. Since 1996, sentinel lymph node mapping has been performed in 100 consecutive patients undergoing colectomy for CRC. Peritumoral injection of 0.5 to 1.0 ml of isosulfan blue dye was performed to demonstrate the sentinel node(s). All lymph nodes in the resection specimen were examined by routine hematoxylin and eosin staining. In addition, a focused examination of multiple sections of the sentinel nodes was performed using both hematoxylin and eosin and cytokeratin immunohistochemical analysis (CK-IHC). Overall, lymphatic mapping successfully demonstrated one to four sentinel lymph nodes in 97 (97%) of 100 patients. These sentinel nodes accurately reflected the status of the nodal basin in 92 (95%) of 97 patients. All five of the false negative cases occurred in T3/T4 tumors, and three of the five occurred during the first 30 cases in the experience. Unexpected lymphatic drainage was encountered in eight patients (8%) and altered the operative approach. Twenty-six patients were node positive by routine hematoxylin and eosin staining. Of the remaining 74 patients with hematoxylin and eosin-negative nodes, an additional 18 patients (24%) were upstaged by identification of occult nodal micrometastases that were missed on routine hematoxylin and eosin staining but detected on multiple sections (n = 5) or by CK-IHC (n = 13). The sentinel lymph nodes were the only positive nodes in 19 cases. Sentinel lymph node mapping may be performed in CRC with a high degree of success and accuracy. A focused pathologic examination of the sentinel node detects micrometastatic disease that is missed by conventional techniques in a significant proportion of patients with early CRC. Further studies are necessary to elucidate the clinical relevance of these micrometastases.