The status of the cervical lymph nodes is the most important prognosticator in head and neck squamous cell carcinoma. The neck dissection is both a therapeutic and staging procedure and has evolved to include various types with standardized level designations (I-VI) for lymph node groups: the radical neck dissection, modified radical neck dissection, the selective neck dissection, and the extended neck dissection. The gross and histologic examination of a neck dissection should provide the critical information (size of metastasis, number of lymph nodes involved) for staging purposes. Additionally, extracapsular spread of lymph node metastasis must be reported because of its significance as an adverse prognosticator. Current dilemmas in nodal disease are the detection of micrometastases, isolated tumor cells, and molecular positivity. The significance of these categories of disease is still unclear, though they may explain a subset of the estimated 10% of the regional recurrences in the neck despite pathologic node negativity by traditional methods of evaluation. Sentinel lymph node biopsy has been recently applied to head and neck squamous cell carcinoma to enhance the management of the clinicoradiographically node negative patients. While still investigational, sentinel lymph node biopsy shows promise in selecting patients who require a neck dissection. Rapid highly automated real-time RT-PCR based platforms will allow for incorporation of molecular findings into the intraoperative evaluation of a sentinel lymph node.