Objective: To explore the diagnosis and treatment of head and neck Castleman′s disease (CD), and to improve the understanding of the disease. Methods: The clinical data of 41 patients with head and neck CD treated from January 2007 to July 2017 in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The patients were divided into two groups: localized CD (LCD, n=27) and multicentric CD (MCD, n=14). The clinical manifestations, laboratory examinations, operations, pathological findings and follow-up data were analyzed. Results: LCD was characterized by asymptomatic enlargement of the single lymph node with mild clinical symptoms. The main pathological type was hyaline vascular type, which can be cured by surgical treatment. MCD accompanied by fever 9 cases(64.3%), anemia 8 cases (57.1%), splenomegaly 7 cases (50.0%), respiratory symptoms 6 cases (42.9%), with multiple enlarged superficial and deep lymph nodes with pain, pleural effusion, and edema of lower extremity, C-reaction protein increased in 8 cases (57.1%), hypoproteinemia 8 cases(57.1%), globulin increased 7 cases (50.0%) and neutropenia 6 cases(42.9%). The main pathological type was plasma cell type in 7 cases (50.0%), and also there were 4 cases of hyaline vascular type and 2 cases of mixed type. Chemotherapy with or without rituximab was the main treatment. Most patients received complete or partial remission except for 2 patients who died of lung infection due to chemotherapy. Conclusions The diagnosis of head and neck CD depends on pathological examination. LCD shows mild symptoms and good prognosis after surgery. However, clinical manifestations of MCD are complex, with relatively poor prognosis after comprehensive treatment.