Copyright © 2021 Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences, and Chinese Medical Association, published by Wolters Kluwer, Inc.Introduction:Numerous dermatoses associated with monoclonal gammopathy have been reported in the literature. Subepidermal autoimmune bullous diseases (SABD) are one of them which were not common.Here we report a case of SABD associated with MGUS who had a severe mucosal involvement and unexpected positive direct Nikolsky phenomenon.Case presentation:A 68-year-old male patient was admitted to our clinic with erosions on the oral mucosa, tense blisters, erosions, and ulcers on the trunk and extremities. Subepidermal vesicle formation was detected in the skin biopsy. Clinical examination revealed positivity for the Nikolsky phenomenon. The disease was unresponsive to conventional treatments and dysphagia and hoarseness occurred. The patient was screened for malignancy due to his unresponsiveness to the treatments and his severe oral mucosal involvement. Ig-G MGUS was detected in the patient.Discussion:The Nikolsky sign is an indicator of acantholysis and is known as a specific finding for pemphigus. However, when we look at gammopathy-associated autoimmune bullous dermatoses, skin fragility has been reported in cases. However, the meaning of fragility is not explained. The diagnosis of all these patients was Ig-M MGUS. Our patient was presented because of non-IgM MGUS, direct Nikolsky positivity, and severe mucosal involvement.Conclusion:Nikolsky positivity may be a clue for gammopathy-related subepidermal autoimmune bullous diseases.