The involvement of the oral mucosa in patients affected by pemphigus vulgaris (PV), paraneoplastic, IgA pemphigus, and in some cases iatrogenic pemphigus is common and often a prelude to skin lesions. Intraepidermal bullae are caused by acantholysis, induced by IgG autoantibodies directed against the desmosomes and the domain of numerous keratinocytes self-antigens desmogleins (namely cadherins), thus supporting the autoimmune nature of the disease. Apoptosis may contribute to the acantholysis. Oral mucosal lesions are more commonly refractory to treatment compared to skin lesions and have been associated with disease duration, disease location and possibly the presence of HSV DNA in the oral cavity. Recent publications have stressed the positive role of Rituximab in early disease treatment.