Mucosal lesions of the upper aerodigestive tract usually concern the squamous epithelium of the surface. Many precancerous alterations now designated as potentially malignant are caused by DNA damage resulting from long term exposure to tobacco and alcohol consumption. The distinction from conditions with a similar phenotype but caused by different reasons such as viral infection may be difficult. Furthermore, a magnitude of similar appearing lesions with different clinical background and different biological behavior are discussed in this paper.