We report a patient with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome who experienced relapse after successful treatment with autologous peripheral blood stem cell transplantation (auto-PBSCT). Interestingly, although vascular endothelial growth factor (VEGF) levels were positively correlated with disease activity before and after auto-PBSCT, as expected, levels did not increase at the time of relapse. The patient was treated with doxorubicin, dexamethasone, and diuretics, followed by thalidomide, and remains clinically stable at one year after treatment. This case suggests that VEGF level may not always be indicative of relapse of POEMS syndrome, and that thalidomide is both useful and safe for patients with relapse following successful treatment with auto-PBSCT.