We present the case of a 71-year-old woman with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. Overproduction of vascular endothelial growth factor (VEGF), secreted by plasmacytoma, is considered responsible for the characteristic symptoms, and therefore anti-VEGF monoclonal antibody (bevacizumab) could be a therapeutic option. The patient was treated with bevacizumab 7 years after onset. Despite a dramatic decrease in serum VEGF levels, there was no clinical improvement, possibly because aberrant angiogenesis had already developed systemically. We suggest that careful consideration should be taken for indication of bevacizumab therapy, and this agent may be used in selected patients with a short duration POEMS syndrome.