Oral cavity cancer is the eighth most common cancer globally with an incidence of 39,400 in the United States in 2011. Over half of the cases diagnosed annually result in a lethal outcome. Surgical resection remains a primary modality for treatment of oral cancers but local and regional recurrence remains the most common problem after surgical resection, resulting in a 60-80% recurrence rate in the first 3 years. Inadequate tumor excision is a common cause for such local recurrence. This could be explained by the current inadequacy of methods for assessing surgical margins and by the presence of satellite malignant cells (skip lesions) in sites away from the primary cancerous lesion, which occur as a result of the field cancerization phenomenon. Current methods for determining a safe surgical margin are highly variable and far from satisfactory. Surgeons often depend on their own judgment or visualization under white light to determine surgical margins. Confirmation of negative margins is often is based on randomly selected samples for frozen-section biopsies, leaving much of the surgical margin unexamined. Moreover, frozen-section analysis can be time consuming, expensive, and have a high false-negative rate. A more accurate and sensitive adjunct to frozen section analysis for the intraoperative detection of safe surgical margins is therefore greatly needed. Optical technologies can be used to distinguish in situ benign from malignant tissue lesions. Elastic Scattering Spectroscopy (ESS) is a point spectroscopic measuring technique that can detect sub-cellular morphological differences between benign and malignant tissue, such as changes in nuclear grade, nuclear to cytoplasm ratio, mitochondrial size and density. ESS provides the advantage of real-time, objective and quick assessment of tissue morphology. Our previous studies using reflectance and fluorescence spectroscopy have shown that spectral measurements can distinguish between benign and dysplastic/malignant lesions when anatomy-based algorithms are applied. This proposed study will explore the feasibility of extending this technique for a new clinical application for oral cancer surgery. We will use it for pre-operative outlining of tumor margin and intra-operative guidance of the surgica excision. Our hypothesis is that ESS measurements can greatly improve surgeons' accuracy in determining and assessing surgical margins in excision of oral cancers compared to traditional approaches alone, thereby significantly reducing local recurrence rates. We will validate our hypothesis in 40 patients undergoing surgery for oral cancer. Our goal is to determine if this optical approach will be able to (1) provide an accurate margin outline before surgery; and (2) guide and improve tumor excision during surgery. This will be the first study of its kind to use this spectroscopic approach for surgery in oral cancers. Our expectation is that it will significantly improve accuracy in surgical resection of oral cancers and reduce recurrence rates. This optical-guided surgery, if successful, will provide surgeons with an ideal tool for margin assessment and will significantly improve prognosis for patients with oral cancer.