Synovial sarcoma (SS) has high metastatic potential and poor prognosis, due to their chemo- and radio-resistance, thus a novel therapy is needed. In order to examine the anti-tumor effect of VEGF targeted therapy against SS, we herein used two human SS cell lines established in our laboratory. These SS cells produced markedly higher level of vascular endothelial growth factor (VEGF) in 3 dimensional (3D) compare to adhesion (2D) cultures. Bevacizumab (Bev), a humanized monoclonal antibody against VEGF, has been approved to clinically improve the prognosis with several malignancies by inhibiting angiogenesis and proliferation of primary and metastatic sites. On the contrary, several studies reported that inhibition of VEGF signal increased tumor invasion and lung metastasis, depending on HIF1α. In soft agar assay, treatment with Bev inhibited the colony formation of these two SS cells, and combination treatment of Bev with Ifosfamide showed higher efficiency. However, proliferation of the two SS cell lines on 2D cultures couldn’t be inhibited by the treatment with Bev. In xenograft models, the combination therapy also effectively reduced the tumor volume without any adverse effect. We are currently focusing on how Bev inhibited tumor growth in 3D but not on 2D. Collectively VEGF-targeted therapy can be proposed as a novel therapy for SS by combination with current chemotherapy.