Project Abstract Approximately 80% of early stage head and neck tumors undergo surgery of curative intent at some point in their treatment course. The success of this oncologic surgery primarily depends on obtaining clear surgical margins. Despite best efforts to obtain wide margins, the surgeon always struggles with removal of healthy, functional tissue. This resulting tension often results in close (<5mm) or positive (tumor at cut surface) margins in 30% of head and neck cancer resections. We have developed a strategy that could improve both intraoperative and ex vivo margin assessment using a fluorescently labeled therapeutic antibody as a targeted imaging agent. We hypothesize that fluorescence imaging of a systemically injected fluorescent anti-epidermal growth factor receptor (EGFR) antibody (EGFR is over-expressed in 80-90% patients with head and neck cancer) will direct the attention of the surgeon and pathologist toward areas that are more likely to be tumor-positive and reduce sampling error. This will lead to improved identification of tumor-positive margins, and thus improved surgical outcome. 1