Indirect fluorescence endoscopy of the larynx has proven to facilitate the detection and delineation of precancerous and cancerous lesion. The different methods are easy to handle and can be performed on an outpatient basis. Early diagnosis of laryngeal cancer and its precursor lesions is simplified. The aim of the present study is to compare indirect autofluorescence laryngoscopy to 5-ALA-induced PPIX fluorescence laryngoscopy. In a prospective study, 56 patients with suspected precancerous or cancerous lesions were primarily investigated by indirect autofluorescence laryngoscopy. In a second step 5-ALA-NaCl (0.6%) was topically applied to the larynx by inhalation, and indirect fluorescence laryngoscopy repeated 2 h after application. Autofluorescence as well as 5-ALA-induced fluorescence was induced by filtered light (375-440 nm) of a xenon short arc lamp and processed by a CCD camera system (D-light-AF System, Storz, Tuttlingen, Germany). White-light and fluorescence images were digitally recorded, immediately assessed for diagnosis and finally compared to pathohistological findings. Inconspicuous laryngeal mucosa presented a typical green fluorescence signal in autofluorescence endoscopy, which turned blue during 5-ALA-laryngoscopy. Precancerous and cancerous lesions displayed a loss of autofluorescence in autofluorescence endoscopy whereas increased protoporphyrin IX fluorescence could be observed in 5-ALA laryngoscopy. Both imaging techniques were suitable to distinguish benign from precancerous or cancerous lesions. In contrast PPIX fluorescence was easily recognized in scarred vocal folds. According to our results, both non-invasive fluorescence imaging techniques are useful in the early diagnosis of laryngeal cancer. Moreover autofluorescence can be used immediately without drug application and possible side effects. 5-ALA-induced fluorescence seems to be more suited for diagnostic examination of mucosal lesions in recurrent precancerous and cancerous lesions after surgery.