We have assessed the value of single fiber reflectance (SFR) spectroscopy in prediction of cervical squamous intraepithelial lesions (SIL). SFR was used to measure reflected light from 32 patients undergoing standard colposcopy. Seven parameters extracted from the spectra in addition to two biographic parameters were compared in biopsy-confirmed SIL versus nonSIL. The significant parameters in the model were determined using stepwise logistic regression. The classification performance was evaluated by a leave-one-out cross-validation method and reported by receiver operating characteristic (ROC) curves. Light absorption properties and biographic characteristics of the patient contributed significantly to the accuracy of the model. Combining important parameters, the best retrospective sensitivity, specificity and area under the ROC curve for SIL sites versus nonSIL were 89%, 80% and 0.89%, respectively. SFR spectroscopy shows promise as a noninvasive, real-time method to guide the clinician in reducing the number of unnecessary biopsies. Discrimination of SIL from other abnormalities compares favorably with that obtained by fluorescence alone and by fluorescence combined with reflectance spectroscopy while the simplicity and low cost of the presented system are dominant.