Oral lesions are conventionally diagnosed using white light endoscopy and histopathology of biopsy samples. Oral lesions are often flat and difficult to visualize under white light illumination. Moreover, histopathology is timeconsuming and there is a need to develop minimally invasive optical biopsy techniques to complement current techniques. Confocal laser endomicroscopy holds promise for virtual biopsy in disease diagnosis. This technique enables fluorescence imaging of tissue structures at microscopic resolution. We have developed a prototype real-time 3- dimensional (3D) imaging system using a laser endomicroscope interfaced with embedded computing. A Field- Programmable Gate Array computing platform has been programmed to synchronize cross-sectional image grabbing and Z-depth scanning, as well as automate acquisition of confocal image stacks. A PC was used for real-time volume rendering of the confocal image stacks. We conducted pre-clinical and pilot clinical studies to image the murine and human oral cavity. High quality volume renderings of the confocal image stacks were generated using 3D texture slicing. Tissue morphology and 3D structures could be visualized. The results demonstrate the potential of the system for diagnostic imaging of the oral cavity. This paves the way toward real-time virtual biopsy of oral lesions, with the aim to achieve same-day diagnosis in a clinical setting.