The diagnosis of head and neck squamous cell carcinoma is usually made by visual identification. Searching for a non-invasive optical diagnostic method with the ability to detect the precancerous lesions or second primary tumors earlier in high-risk populations led to the development of photodiagnosis by autofluorescence (AF) endoscopy. The aim of the present study was to evaluate and discuss the diagnostic potential of autofluorescence videoendoscopy as a complementary visual aid in the routine endoscopic diagnosis of head and neck cancers. In a prospective study, 48 patients underwent white light (WL) videoendoscopy followed by AF technique at the Institute of Gustave-Roussy from November 2001 to August 2002. Of 48 patients, 30 had suspected precancerous or cancerous laryngeal lesions, 7 presented benign laryngeal lesions, while 8 showed pharyngeal and 3 oral tumors. All detected lesions were evaluated by histological examination. AF was induced by filtered blue light of a xenon short arc lamp and processed by a CCD camera system (D-Light AF System; Storz, Tuttlingen, Germany). Normal laryngeal mucosa displayed a typical green fluorescence signal. Moderate and severe epithelial dysplasia, carcinoma in situ and invasive carcinoma showed a diminished green fluorescence and presented a marked reddish-blue color. In case of hyperkeratosis a bright white color was detected. Some benign lesions, such as granulomas, polyps and papillomas also displayed altered green fluorescence. Autofluorescence videoendoscopy for photodiagnosis of head and neck squamous cell carcinomas has proved to be a method of high specificity and good sensitivity. Two additional precancerous lesions that were invisible at the WL examination but detected with the AF technique show its potential role in the regular screening procedure or follow-up examination in a high-risk population. It was a very helpful complementary visual aid for the intraoperative control of the surgical margins after per oral endoscopic resection.