The prognosis for patients with oral squamous cell carcinoma remains poor despite advances in multimodal treatment concepts. Early diagnosis and treatment is the key to improved patient survival. A device (VELscope) that uses autofluorescence technology, allowing direct fluorescence visualization of the oral cavity, might be a useful tool for oral cancer detection or as an adjunct to standard clinical examination. A total of 289 patients with oral premalignant lesions were randomly divided into two groups for clinical examination of precancerous oral lesions. In group 1, 166 patients were examined conventionally with white light, and in group 2, 123 patients were examined with the autofluorescence visualization device (VELscope) in addition to the white light examination. Biopsies were obtained from all suspicious areas identified in both examination groups (n=52). In the first step, baseline characteristics of the two groups (only white light vs. white light and VELscope) were compared to exclude selection bias. In the second step, for the group examined with white light and VELscope (123 patients), the diagnostic strategies were compared with regard to sensitivity and specificity using biopsy as the gold standard. The results showed that using the VELscope leads to higher sensitivity (100% instead of 17%), but to lower specificity (74% instead of 97%). Thus, we can conclude that the VELscope is a useful new diagnostic device for detection of oral cancer diseases.