Purpose To portray a rare dermatological autoimmune condition masquerading clinically and pathologically as a lip mucosal squamous cell carcinoma (SCC). Methodology This is a case study of a 70-year-old female referred with a biopsy proven dysplastic squamoproliferative lesion involving the right lower lip clinically concerning for a squamous cell carcinoma. Patient had risk factors of prolonged sun exposure, smoking and had previous skin cancers. Results A vermilionectomy with mucosal advancement was performed excising the lower lip lesion of concern. Pathological examination confirmed a SCC in situ involving the peripheral margins. Four weeks following the initial operation the patient displayed further lower lip ulceration. Further treatment with Fluorouracil 5% cream did not yield any improvement. A second biopsy was performed showing severe acantholytic dermatitis. Following further pathological assessment of the primary excision with aid of immunohistochemistry, the diagnosis was reconsidered. Desmoglein-3 auto-antibodies were detected confirming the diagnosis of mucosal predominant pemphigus vulgaris. The patient was referred to a dermatology unit and started on mycophenolate and diprosone ointment. Conclusion Pemphigus vulgaris is a rare auto-immune dermatological conditions with autoantibodies that target keratinocyte proteins. The disease is marked macroscopically by ulceration and bullae formation and microscopically by loss of keratinocyte-to-keratinocyte adhesion and thus acantholysis. Subsets of the disease show mucosa predomination. This case portrays the importance of considering differential diagnosis in cases of unusual post operative course as well the as importance of involvement of multi-disciplinary team.