Vesiculobullous diseases are immunologically mediated disorders that cause blisters, erosion and erythema of both skin and mucous membranes. They are uncommon clinicopathologic syndromes whose diagnosis depends on identification of characteristic causative agent and clinicopathologic features. None of the histopathologic patterns of vesiculobullous conditions is absolutely specific for any of them. For a variety of reasons, these conditions represent the most difficult challenge for clinical diagnosis. Bullous diseases can mimic one another clinically and histologically. These lesions are quite distinctive in early stages, but after “blisters” rupture and disappear, the resultant ulcerative lesion is quite non-specific in appearance. Originally surrounded by red rims these lesions appear white, while the vesicles or blebs are intact. When the blebs fully rupture and become emptied, their white appearance usually disappears. In the oral cavity both vesicle and bullae are more flattened, with a smooth gelatinous surface. When attempting to differentiate between a vesicular from a bullous lesion, the size of the individual lesion is the key to diagnosis.