Oral lichen planus (OLP) occurs in from 2% to 3% of the population and may have a risk of malignant transformation into squamous cell carcinoma (SCC). This risk is not necessarily associated with exposure to tobacco and alcohol. An increased awareness of a possible role of human papilloma virus (HPV) and SCC led us to review a possible association between this virus infection and malignant transformation of OLP. The possible linkage between HPV and the risk of transformation of OLP to malignancy is discussed. Furthermore, management of OLP using immunosuppressive drugs may be associated with enhanced viral replication and could theoretically affect the risk of malignant transformation. Implications for clinical care are discussed.