Sentinel node biopsy for head and neck squamous cell carcinoma seems to be able to accurately stage the cN0 neck and to select patients who benefit from elective neck dissection. The goal of sentinel node biopsy is to avoid unnecessary neck dissections in clinically N0 patients and thus decrease patient morbidity and health care costs. The average rate for detecting a sentinel node with lymphoscintigraphy and the intraoperative use of a handheld gamma probe is 95% to 100%. In the head and neck region, where lymphatic drainage patterns are of greater complexity and the primary sites close to the first-echelon node, integrated single-photon emission computed tomography (SPECT)–computed tomography (CT) imaging is thought to be of value in that it provides the surgeon with a more accurate roadmap by precisely defining the drainage basins and the sentinel node localization. SPECT-CT enhances topographic orientation and diagnostic sensitivity, with more sentinel nodes being detectable than by planar lymphoscintigraphy alone. We suggest that planar imaging should be accompanied by iterative reconstructed SPECT-CT to identify lymph nodes adjacent to the primary lesion. Such nodes are easily overlooked by planar lymphoscintigraphy and intraoperative gamma probes, as the high activity at the injection site can obscure their detection (see Fig. 35.1).