Objective To determine the clinical and prognostic features in CD56 negative multiple myeloma (MM) patients. Methods By reviewing and analyzing the clinical and laboratory data of 48 new cases of MM patients，we compared the clinical and prognostic features between CD56 negative ( CD56- ) MM patients and CD56 positive (CD56 + ) MM patients. Results Among 48 MM cases, 14 patients(29% ) were CD56 negative while 34 patients (71% ) were CD56 positive. There were no significant differences between the two groups in age，gender and clinical stage. Common symptoms of the two groups included bone pain，osteoporosis，pathologic fracture，anemia and infection. Among all these symptoms，the rate of bone pain was higher in CD56 + patients than that of CD56- patients ( P < 0. 05 ) . There were no other notable differences both on clinical manifestations and onset of disease. No significant differences were shown on disease progress parameter，such as hemoglobin level，platelet number， serum calcium level， and albumin level (P >0.05). No notable differences involved in the analysis of prognostic factors between the two groups，such as bone marrow plasma cell number， p2_MG，CRP and ESR. The rate of the multiple bone destruction was obviously lower in CD56-MM than that of CD56 + MM(64. 3% vs 91. 2%，P <0. 05) . The median survival time was 14. 7 months in CD56 negative patients while 15 months in CD56 positive patients. No significant differences was shown on the overall survival(P =0.348). Conclusion By comparing CD56 negative and CD56 positive patients，there are no significant differences in clinical and prognostic features.