Objectives: To determine the feasibility and accuracy of the Niris Optical Coherence Tomography (OCT) system in imaging of the mucosal abnormalities of the head and neck. The Niris system is the first commercially available OCT device for applications outside ophthalmology. Methods: We obtained OCT images of benign, premalignant and malignant lesions throughout the head and neck, using the Niris OCT imaging system (Imalux, Cleveland, OH). This imaging system has a tissue penetration depth of approximately l-2mm, a scanning range of 2mm and a spatial depth resolution of approximately 10-20μm. Imaging was performed in the outpatient setting and in the operating room using a flexible probe. Results: High-resolution cross-sectional images from the oral cavity, nasal cavity, ears and larynx showed distinct layers and structures such as mucosa layer, basal membrane and lamina propria, were clearly identified. In the pathology images disruption of the basal membrane was clearly shown. Device set-up took approximately 5 minutes and the image acquisition was rapid. The system can be operated by the person performing the exam. Conclusions: The Niris system is non invasive and easy to incorporate into the operating room and the clinic. It requires minimal set-up and requires only one person to operate. The unique ability of the OCT offers high-resolution images showing the microanatomy of different sites. OCT imaging with the Niris device potentially offers an efficient, quick and reliable imaging modality in guiding surgical biopsies, intra-operative decision making, and therapeutic options for different otolaryngologic pathologies and premalignant disease. © 2009 SPIE.