ABSTRACT No real-time quantitative devices are clinically used to assess oral lesions during routine examination, making in-clinic diagnostic and longitudinal monitoring challenging. Instead, lesions are evaluated through visual inspection and then histopathological analysis of tissue samples extracted during biopsy. Identifying premalignant and malignant oral lesions early is critical to ensuring effective treatment is provided to patients with malignancies. Oral cancer currently has one of the lowest 5-year survival rates (50% or less) among major cancer types, largely due to the challenges in identifying premalignant and malignant lesions early. Clearly, a real-time in-clinic device able to classify oral lesions as benign, premalignant, or malignant has the potential to provide immediate impact to patient care. Significantly different electrical property signatures have been observed between benign and malignant tissues in a variety of organs, including tongue; since the bioelectrical properties are so dependent on tissue architecture and morphology, we hypothesize that sensing and imaging these properties in the context of oral lesions will enable us to accurately characterize and classify morphologically-different benign, premalignant, and malignant oral lesions. We have developed an endoscopic electrical impedance imaging (EII) device for use in intraoperative surgical margin assessment that we aim to optimize for in-clinic oral lesion assessment. We aim to take the significant step of translating our extensive experience in impedance imaging to develop an oral lesion imaging device that can be deployed safely, and in the clinic, to provide real-time feedback regarding oral lesion classification. We propose constructing a novel chip-on-tip EII probe to sense and image at near microscopic resolution oral lesions in an effort to provide clinicians with real-time, accurate classification of oral lesion pathology that can be used for diagnostic and longitudinal monitoring purposes. The probe will be evaluated on a series of in vivo human oral lesions and compared with histopathological analysis of biopsy samples. The low-cost of a device such as this makes it an ideal technology for low-resource settings and the safety and real-time capabilities of the system make it ideal for continuously following lesions.