Many conditions that affect the oral mucosa along with other mucosal sites are either autoimmune or immunologically mediated. They include pemphigus, mucous membrane pemphigoid (MMP), lichen planus, aphthous stomatitis, linear IgA, bullous dermatosis, dermatitis herpetiformis, and epidermolysis bullosa acquisita (EBA). The clinical manifestations include vesicles, bullae, erosions, and ulcers. Oftentimes, both the clinical and histopathological features of some of these conditions overlap, thereby making even more sophisticated methods necessary for accurate diagnosis (Table 1). Because both the clinical presentation and the immunology of the disease can be critical in making the correct diagnosis, both areas are addressed, along with the pathology of vesiculoerosive and ulcerative lesions of the oral mucosa.