Differentiating between early malignancy and benign lesions in oral cavities is difficult using current optical tools. As has been shown in previous studies, microvascular changes in squamous epithelium can be regarded as a key marker for diagnosis. We propose the combination of structural and vascular optical coherence tomography (OCT) imaging for the investigation of disease related changes. Progressive thickness changes of epithelium and the destruction of underlying lamina propria was observed during cancer development in a 4- nitroquinoline-1-oxide (4NQO) mouse model. At the same time, microvascular changes in hyperplasia, dysplasia, carcinoma in situ and advanced cancer were observed. Findings from OCT imaging were compared with histology.