Desquamative gingivitis (DG) is a descriptive term for lesions of the attached and marginal gingiva characterized by epithelial desquamation, erythema, erosion, and/or vesiculobullous formations, and DG is commonly associated with a variety of mucocutaneous and systemic disorders. Thus, in many cases, dentists would be the first health care professionals to identify these symptoms in the oral cavity. To distinguish DG from plaque-induced gingivitis, a condition that is incredibly common and is easily diagnosed and treated every day, it is critical to be aware of this uncommon clinical entity. Early detection of these lesions may help to avoid delayed diagnoses and ineffective therapies for diseases that have the potential to be very serious.