Pemphigus vulgaris (PV) is an autoimmune disease, characterized by the formation of autoantibodies against desmosomes of keratinocytes, resulting in intraepithelial blisters. We report a case of a 70-year-old female patient presenting with widespread, painful, eroded, or ulcerated mucosal lesions with 3 weeks’ evolution. Nikolsky’s sign was negative. Incisional biopsy of a jugal mucosa lesion was performed, and histopathologic analysis revealed squamous epithelium showing acantholysis, with suprabasal clefts containing so-called acantholytic Tzanck cells. The diagnosis was PV, confirmed by direct immunofluorescence. Prednisolone (60 mg/once/daily) was prescribed for 15 days, with improvement of the condition, and further gradual dose reduction was carried out. The patient is undergoing follow-up for 20 months, with no oral or cutaneous manifestation of the disease. Although PV is a systemic disorder, oral manifestations often precede cutaneous manifestations and are the first signs of disease. Thus, dentists have a fundamental role in the early diagnosis and treatment of these conditions. Pemphigus vulgaris (PV) is an autoimmune disease, characterized by the formation of autoantibodies against desmosomes of keratinocytes, resulting in intraepithelial blisters. We report a case of a 70-year-old female patient presenting with widespread, painful, eroded, or ulcerated mucosal lesions with 3 weeks’ evolution. Nikolsky’s sign was negative. Incisional biopsy of a jugal mucosa lesion was performed, and histopathologic analysis revealed squamous epithelium showing acantholysis, with suprabasal clefts containing so-called acantholytic Tzanck cells. The diagnosis was PV, confirmed by direct immunofluorescence. Prednisolone (60 mg/once/daily) was prescribed for 15 days, with improvement of the condition, and further gradual dose reduction was carried out. The patient is undergoing follow-up for 20 months, with no oral or cutaneous manifestation of the disease. Although PV is a systemic disorder, oral manifestations often precede cutaneous manifestations and are the first signs of disease. Thus, dentists have a fundamental role in the early diagnosis and treatment of these conditions.