This paper deals with the development and application of in vivo spatially-resolved bimodal spectroscopy(AutoFluorescence AF and Diffuse Reflectance DR), to discriminate various stages of skin precancer in a preclinicalmodel (UV-irradiated mouse): Compensatory Hyperplasia CH, Atypical Hyperplasia AH and Dysplasia D. A programmableinstrumentation was developed for acquiring AF emission spectra using 7 excitation wavelengths:360, 368, 390, 400, 410, 420 and 430 nm, and DR spectra in the 390–720 nm wavelength range. After various steps of intensityspectra preprocessing (filtering, spectral correction and intensity normalization), several sets of spectralcharacteristics were extracted and selected based on their discrimination power statistically tested forevery pair-wise comparison of histological classes. Data reduction with Principal Components Analysis (PCA)was performed and 3 classification methods were implemented (k-NN, LDA and SVM), in order to compare diagnosticperformance of each method. Diagnostic performance was studied and assessed in terms of sensitivity (Se) andspecificity (Sp) as a function of the selected features, of the combinations of 3 different inter-fibers distances and of thenumbers of principal components, such that: Se and Sp≈ 100% when discriminating CH vs. others; Sp≈ 100% and Se> 95% when discriminating Healthy vs. AH or D; Sp≈ 74% and Se≈ 63% for AH vs. D.