Background: Oral Lichen planus (OLP) is one of the most common oral diseases that has an unneglectable rate of malignant transformation. Recently malignant transformation has been definitively linked to epigenetic changes. One of those most common changes is DNA hypermethylation that causes tumor suppressor genes to downtranslate and thus carcinogenesis begins. ZNF582 gene hypermethylation is emerging as an exclusive biomarker to differentiate between normal and dysplastic changes that occur over the epithelium. Aim: To evaluate the Melatonin epigenetic potential in preventing malignant transformation of OLP. Material and methods: an epigenetic randomized clinical study will be conducted on 50 patients suffering from OLP, recruited from the outpatient clinic of Oral medicine department, Alexandria Faculty of Dentistry, Egypt. Patients will be assigned to either Control group who will receive topical corticosteroids and antifungal treatment, or test group who will receive melatonin supplement in addition to conventional treatment. All patients will be genetically evaluated for the level of DNA hypermethylation 8 weeks after treatment, and clinically evaluated for disease severity and pain, by Elsabagh scoring system 4. 8, and 12 weeks after treatment.

Inclusion Criteria:

• Patients clinically and histopathologically diagnosed to be suffering from OLP in the following forms has been reported in the literature to have the highest potentiality for malignant transformation (plaque-type lichen , Erosive lichen planus, ulcerative lichen planus), with or without histopathological dysplasia.
• Patients who have symptoms (i.e. pain and burning sensation) secondary to OLP.

Exclusion Criteria:

• Patients suspected to have lichenoid drug reaction or lichenoid contact allergy.
• Patients suffering from systemic diseases (such as diabetes, cardiovascular or liver disorders, renal dysfunction).
• Patients with findings of any physical or mental abnormality that would interfere with or be affected by the study procedure.
• Patients who have adverse habits of chewing tobacco and smoking.
• Pregnant and lactating women.
• Patients under treatment with corticosteroids and immunosuppressants.
• Patients exhibiting any skin manifestations of OLP