Abstract: Objective To investigate whether vasculogenic mimicry（VM） was present in osteosarcoma and its relevance with patients' clinicopathologic features and prognosis. Methods VM was assessed in osteosarcoma by CD34／PAS doublestaining of specimens from 66 patients. VM channels were verified to be of osteoblastic origin by staining for osteonectin and osteocalcin， and tumors were also immunohistochemically stained for focal adhesion kinase（FAK） and migration inducing gene-7（Mig-7） to determine whether these markers are associated with the occurrence of VM. The relevance of VM with the prognosis was also investigated. Results VM was observed in 15 of the 66 osteosarcoma samples（22.7％）， and the incidence of VM didn't differ with respect to patient sex， age， tumor size， tumor site， surgical type or histological response to pre-operative chemotherapy. However， Kaplan-Meier survival analysis determined that the presence of VM and the tumor necrosis rate after preoperative chemotherapy were associated with both the overall survival（P=0.011 and 0.040， respectively） and metastasis-free survival（P=0.002 and 0.045， respectively）. Furthermore， Cox proportional hazards analysis showed that the presence of VM and the histological response to preoperative chemotherapy were independent indicators for both poor overall survival（P=0.007 and 0.024， respectively） and poor metastasis-free survival（P=0.002 and 0.027， respectively）. The expression level of FAK and Mig-7 were higher in VM group than nonVM group（P=0.017 and 0.021， respectively）. Conclusion These results demonstrate the presence of VM in osteosarcoma and suggest that VM is an unfavorable prognostic factor with FAK and Mig-7 expression as a potential associated mechanism of VM formation in osteosarcoma.