Differential path-length spectroscopy (DPS) was used to non-invasively determine the superficial optical properties of oral mucosa in vivo. DPS yields information on physiological parameters such as the mucosal blood content, the microvascular blood oxygenation and the average micro-vessel diameter as well as on morphological parameters such as the scattering slope and scattering amplitude. DPS measurements were made on normal and cancerous oral mucosa using a novel fiber-optic probe, and were correlated to the histological outcome of punch biopsies taken from the same location. Our data shows that the mucosa of oral squamous cell carcinoma is characterised by a significant decrease in microvascular oxygenation and increase in mucosal blood content compared to normal oral mucosa as well as a significant decrease in scattering amplitude and increase in scattering slope.