Oral mucosal desquamation is a common manifestation of a number of pathologic conditions. The differential diagnoses may range from chemical and electrical burns to conditions such as allergic reactions, hormonal disorders, and mucocutaneous conditions. This article reports two cases of oral mucosal reactions that became a diagnostic challenge at the time of examination. Both subjects had chronic extensive desquamative stomatitis and gingival ulcerations. Following a careful review of their medical and dental history, the use of oral health care products was projected as a possible cause of their mucosal condition.