A low-cost, fast, and noninvasive method for early diagnosis of malignant lesions of oral mucosa based on diffuse reflectance spectral signatures is presented. In this technique, output of a tungsten halogen lamp is guided to the tissue through the central fiber of a reflection probe whose surrounding six fibers collects tissue reflectance. Ex vivo diffuse reflectance spectra in the 400 to 600-nm region is measured from surgically removed oral cavity lesions using a miniature fiber optic spectrometer connected to a computer. Reflectance spectral intensity is higher in malignant tissues and shows dips at 542 and 577 nm owing to absorption from oxygenated hemoglobin (HbO2). Measurements carried out, within an hour of surgical excision, on malignant lesion and adjoining uninvolved mucosa show that these absorption features are more prominent in neoplastic tissues owing to increased microvasculature and blood content. It is observed that reflectance intensity ratio of hemoglobin bands, R540/R575, from malignant sites are always lower than that from normal sites and vary according to the histological grade of malignancy. The diffuse reflectance intensity ratio R540/R575 of the hemoglobin bands appears to be a useful tool to discriminate between malignant lesions and normal mucosa of the oral cavity in a clinical setting.