Abstract: Objective Multiple myeloma (MM) often leads to many parts of osteoporosis and focal bone destruction. Especially simple vertebral compression fractures are easily misdiagnosed as osteoporotic vertebral fracture (OVCF),through the comparative analysis of two different kinds of disease in the aspect of clinical characteristics and content of β2–microglobulin are helpful for the early diagnosis and treatment planning. Methods A total of 40 patients with osteoporosis vertebral compression fracture were admitted to the hospital from October 2009 to May 2016 , including 20 patients with OVCF (control group), 20 patients with diagnosis of MM (observation group).To explore the clinical characteristics and differences of β2–microglobulin, so as to provide clinical reference for early diagnosis. Results All the 40 patients presented with vertebral osteoporosis fracture, and none of them had extraspinal bone destruction. Some cases in the observation group had characteristic fracture area, and the level of β2–microglobulin was significantly higher than that in the control group, with statistically significant difference (P<0.05). The optimal cutoff value of serum β2-MG for the diagnosis of MM was 3.08 mg/L (sensitivity was 85.0%, specificity was 85.0%). Conclusion Serum β2-MG is one of the sensitive indicators for the diagnosis of MM. For patients with osteoporotic vertebral compression fractures, an abnormally high β2-MG should be observed, and the possibility of MM should be highly considered.