Optical spectroscopy may be used for in vivo, noninvasive distinction of malignant from normal tissue. The aim of our study was to analyze the accuracy of various optical spectroscopic techniques for the classification of cancerous lesions of the bronchial tree. We developed a fiberoptic instrument allowing the measurement of autofluorescence spectroscopy (AFS), diffuse reflectance spectroscopy (DRS), and differential path length spectroscopy (DPS) during bronchoscopy. Spectroscopic measurements were obtained from 191 different endobronchial lesions (63 malignant and 128 nonmalignant) in 107 patients. AFS, DRS, and DPS sensitivity/specificity for the distinction between malignant and nonmalignant bronchial lesions were 73%/82%, 86%/81%, and 81%/88%, respectively. All three optical spectroscopic modalities facilitate an increase of the positive predictive value of autofluorescence bronchoscopy for the detection of endobronchial tumors. Even better results were obtained when the three spectroscopic techniques were combined.