Abstract: Paraneoplastic pemphigus (PNP) is a tumor-related autoimmune disease affecting the skin and mucosa, while the occurrence of mediastinal giant thymoma with PNP is infrequent in clinical practice. In this study, the authors presents a case of PNP and conducts a comprehensive analysis of its clinical, histopathological, therapeutic, and ¹⁸F-fluorodeoxyglucose (FDG) PET/CT imaging characteristics, thereby deepening the understanding of this disease through literature review. The possibility of PNP should be considered in patients with polymorphic skin lesions, the diagnosis of which is based on clinical presentation, histopathologic examination, and immunofluorescence. The autors found occult malignant tumors by PET/CT imaging, which assisted clinicians to understand the intrinsic connection between thymoma and PNP, improved the diagnostic accuracy of preoperative diagnosis, and provided an important basis for the choice of treatment plan.