Oral biopsy of vesiculobullous diseases such as pemphigus vulgaris often raises questions due to some particularities involving this procedure. The adequate selection of the area to be biopsied defines if the final diagnosis will be reached, being the Achiles heel of the proper management of the patient. Here, the authors report a case of a woman who sought for treatment of generalized oral blisters and ulcers that caused severe pain. She had undergone a previous biopsy by other professionals that was inconclusive. The authors’ team diagnosed the patient with pemphigus vulgaris and treated her properly. The authors provide a brief discussion about the adequate oral site to be chosen when dealing with vesiculobullous diseases once it still remains a source of doubts for the dental surgeons.