Aim: The aim of this case presentation was to highlight the importance of the awareness of two different coexisting pathologies, as well as emphasise that early diagnosis and prompt management are essential to manage pemphigus vulgaris. Pemphigus vulgaris is a rare, life-threatening autoimmune disease characterised by the presence of blisters on the surface of oral mucosa caused by antibodies against adhesion molecules on the cell surface of keratinocytes. Coexistence with various conditions, notably herpes simplex virus, is noteworthy. Case report: We report a case of a middle-aged female who presented with non-healing oral ulceration that turned out to be herpes simplex virus, consequently triggering pemphigus vulgaris. Histopathology and immunofluorescence were suggestive of pemphigus vulgaris, but immunohistochemistry and polymerase chain reaction were indicative of herpes simplex virus infection. Conclusion: The coexistence of a viral infection with pemphigus vulgaris poses a therapeutic challenge.