In maxillofacial surgery, there are periodic cases of long-lasting chronic inflammation of the soft tissues without the positive effect of the conservative treatment. In these cases, questions arise of a detailed analysis of the etiology and pathogenesis of the disease, differential diagnosis of the pathological process, including those rarely encountered in the practice of a maxillofacial surgeon. One of these diseases is Rosai Dorfman’s disease, which refers to extranodal histiocytosis. In domestic and foreign literature, single clinical observations are found without a detailed analysis of the diagnostic algorithm and the choice of treatment tactics. This article presents a clinical case of Rosai—Dorfman disease of a 55-year-old patient with a lesion of the soft tissues of the maxillofacial region. The described case took place in the clinic of maxillofacial surgery of the Research Institute of Dentistry of Surgical and Maxillofacial Surgery PSPbGMU named after academician I.P. Pavlova in the period from 2016 to 2019. Given the complexity of the diagnosis of this rare nosological form, we offer a specific examination algorithm that leads to a multidisciplinary comprehensive approach from disease verification to the choice of treatment tactics.