Project Abstract In patients with primary squamous cell carcinoma of the head and neck, the presence of lymph node metastasis is considered the most important negative prognostic factor for survival. Despite advanced anatomic and metabolic imaging techniques, in patients staged clinically and radiographically as node-negative (cN0), occult lymph node metastasis are still present in 20-30% of patients. To address this, the current guidelines recommend either elective regional neck dissection or sentinel lymph node biopsy. Compared to a neck dissection, minimally- invasive sentinel lymph node biopsy minimizes surgical morbidity, cosmetic deformity, and duration of surgery. unfortunately, the sentinel lymph node biopsy technique has not been widely adopted in head and neck cancer because the tumors are often inaccessible and patients poorly tolerate direct tumor injections (the current standard of care). To facilitate the adoption of this minimally-invasive technique in routine clinical practice the United States, we propose to overcome these traditional barriers to sentinel lymph node biopsy using a systemically delivered agents to replace locally injected agents. To this end, we propose a pilot study in head and neck cancer patients to determine if the presence of radio- or fluorescence-labeled panitumumab correlates with histological evidence of cancer in surgically obtained lymphadenectomy samples. If successful, our study would be the first trial to evaluate the use of a systemic imaging agent for sentinel lymph node biopsy identification and removal. Successful application of this technique to head and neck cancers could have implications for other tumor types for which lymph node status plays an important role.