Oral squamous cell carcinoma is the most common form of malignancy of the oral cavity; its incidence is increasing and late-stage presentation is common. It is usually predated by oral premalignant disorders. For this reason, early diagnosis is fundamental to reduce the malignant transformation of oral premalignant disorders and for increase the survival rate for oral cancer. Scraping the surface of the lesion is useful for having cytological features of the investigated tissue. The features of smears of oral premalignant lesions are the keratinization growth (red, orange, brown), the increased nuclear area and so the nuclear hyperchromatism, the nuclear pleomorphism, and the chromatin clumping. All those features are essential for doing the right diagnosis. However, the oral disease should be recognized at the first view by the clinical investigation without touching the lesions avoiding possible alteration in the cells of the tissue. The current standard of incisional biopsy with histology is painful for patients and involves a delay, although histology is completed. The aim of this article is to evaluate the effectiveness of other available tests that are unobtrusive and provide immediate results like the tissue fluorescence imaging.