The Rosai-Dorfman disease (RDD) is a kind of sinus histiocytosis with massive lymphadenopathy and is remarkably rare. RDD is characterized by large histiocytes with emperipolesis. However, the cause of RDD is unknown, and most cases are relieved spontaneously. In rare cases, patients may have onset and remission of lymph nodes and extranodal involvement. This report showed an RDD case in a 67-year-old male patient with systemic superficial lymphadenopathy and high IgG4 plasma cell infiltration. We showed that a possible RDD diagnosis should be kept in mind when encountering a systemic multiple lymphadenopathy and high IgG4 plasma cell infiltration. Also, an overlap between RDD and IgG4-related disease might be present, which might help in clinical recognition of RDD.