Objective: To explore the detection methods and transfusion strategies of autoantibodies with specificity against Rh blood group system to provide timely and effective transfusion treatment for those patients. Methods: A case of a patient with autoantibodies with anti-Ce specificity was studied through serological tests, including ABO and Rh blood group identification, Coombs tests, antibody identification test and acid elution test. PCR-SSP was carried out to identify the Rh phenotype. The cross-matching test should avoid the specificity of anti-Ce autoantibody. The hemoglobin was measured pre- and post- the transfusion. Results: The results of the serological tests showed the blood group of the patient was AB type, RhD positive, and Rh blood group was CcEe before transfusion Direct antiglobulin test (DAT), and indirect antiglobulin test (IAT) were positive. According to the identification of antibodies, there were autoantibodies with anti-Ce specificity in the patient’s serum. The Rh antigen phenotyping was C⁺, c⁺, E⁺, e⁺ through the gene analysis. The results of the cross-matching were negative and the blood group of the red blood cell were AB, ccDEE. The hemoglobin of the patient increased from 48 g/L to 60 g/L and 58 g/L to 88 g/L rapidly after transfusion. Conclusions: In rare cases, autoantibodies can also show the characteristics of the complete antibodies rather than the pattern which could be agglutination with all the red blood cells for antibodies identification but there were strength differences. During blood transfusion treatment for those patients, we should try to avoid the specificity of autoantibodies, and carry out cross matching test before transfusion. After the titter of the autoantibodies decreased or disappeared, homotypic red blood cells for transfusion could be carried out.