The clinical utility of sentinel node biopsy techniques for cutaneous melanoma has led multiple investigators to study the applicability of this approach to other solid tumors, including cancers of the upper aerodigestive tract, and especially the oral cavity. Preliminary data indicate that it may be useful for early oral cancers, with the exception of floor of mouth tumors, where technical challenges related to the proximity of the lymphatic basin remain a problem. A multi-institutional pathologic validation trial, involving sentinel node biopsy followed by completion selective neck dissection, has completed accrual. While central step sectioning and immunohistochemistry remain to be completed and analyzed, routine pathologic techniques provided negative predictive values of 96% for oral cancer excluding floor of mouth lesions. Subsequent trials need to involve clinical follow-up and evaluation for recurrence in the neck. We believe this technique may ultimately play a role in the management of early oral cancer.