Abstract: The present invention provides a new method and device for disease detection, more particularly cancer detection, from the analysis of diffuse reflectance spectra measured in vivo during endoscopic imaging. The measured diffuse reflectance spectra are analyzed using a specially developed light-transport model and numerical method to derive quantitative parameters related to tissue physiology and morphology. The method also corrects the effects of the specular reflection and the varying distance between endoscope tip and tissue surface on the clinical reflectance measurements. The model allows us to obtain the absorption coefficient (?a) and further to derive the tissue micro-vascular blood volume fraction and the tissue blood oxygen saturation parameters. It also allows us to obtain the scattering coefficients (?s and g) and further to derive the tissue micro-particles volume fraction and size distribution parameters.