The performance of a fluorescence imaging device was compared with conventional white-light bronchoscopy in 100 patients with lung cancer, 46 patients with resected stage I non-small cell lung cancer, 10 patients with head and neck cancer, and 67 volunteers who had smoked at least 1 pack of cigarettes per day for 25 years or more. Using differences in tissue autofluorescence between premalignant, malignant, and normal tissues, fluorescence bronchoscopy was found to detect significantly more areas with moderate/severe dysplasia or carcinoma in situ than conventional white-light bronchoscopy with a similar specificity. Multiple foci of dysplasia or cancer were found in 13-24% of these individuals. Fluorescence bronchoscopy may be an important adjunct to conventional bronchoscopic examination to improve our ability to detect and localize premalignant and early lung cancer lesions.