The clinical utility of sentinel node biopsy for melanoma has led multiple investigators to apply this approach to other cutaneous malignancies as well as to early cancers of the upper aerodigestive tract. Data are most extensive for oral cancer. A multi-institutional pathologic validation trial for selected oral cancers provided negative predictive values of 96%. Subsequent trials should document clinical follow-up. This technique may ultimately play a wider role in the management of mucosal cancers.