Overview: Although the agreed-upon standard is circumferential pathology analysis of the interface between the resected specimen and the patient, there is currently no consensus on the optimal methodology to achieve this in head and neck cancer specimens. This is most commonly conducted by either sampling the wound bed after resection or obtaining samples from the specimen. Regardless of the technique, only a fraction of the area of interest can be sampled due to the labor-intensive nature of frozen sections. Objective: This review will cover and define the possible role for optical mapping of the surgical specimen using fluorescence imaging in head and neck cancer. Level of Evidence: NA.