Keywords autofluorescence spectroscopy ¿ cancer detection ¿ combined classifiers ¿ oral cancer ¿ reflectance spectroscopy Abstract Background and Objectives Autofluorescence and diffuse reflectance spectroscopy have been used separately and combined for tissue diagnostics. Previously, we assessed the value of autofluorescence spectroscopy for the classification of oral (pre-)malignancies. In the present study, we want to determine the contributions of diffuse reflectance and autofluorescence spectroscopy to diagnostic performance. Study Design/Materials and Methods Autofluorescence and diffuse reflectance spectra were recorded from 172 oral lesions and 70 healthy volunteers. Autofluorescence spectra were corrected in first order for blood absorption effects using diffuse reflectance spectra. Principal Components Analysis (PCA) with various classifiers was applied to distinguish (1) cancer and (2) all lesions from healthy oral mucosa, and (3) dysplastic and malignant lesions from benign lesions. Autofluorescence and diffuse reflectance spectra were evaluated separately and combined. Results The classification of cancer versus healthy mucosa gave excellent results for diffuse reflectance as well as corrected autofluorescence (Receiver Operator Characteristic (ROC) areas up to 0.98). For both autofluorescence and diffuse reflectance spectra, the classification of lesions versus healthy mucosa was successful (ROC areas up to 0.90). However, the classification of benign and (pre-)malignant lesions was not successful for raw or corrected autofluorescence spectra (ROC areas@en