POEMS syndrome is a complex and rare hematological disease involving multiple physiological systems. According to the currently accepted diagnostic criteria for POEMS syndrome, polyneuropathy is one of the primary mandatory criteria. A patient presented with M protein, Castleman disease (CD), elevated vascular endothelial growth factor (VEGF), extravascular volume overload, and endocrinopathy. However, edema of the extremities hindered the diagnosis of polyneuropathy by electromyography (EMG). Eventually, we diagnosed the patient with atypical POEMS syndrome without polyneuropathy. The case also exhibited features consistent with TAFRO syndrome, such as anasarca, thrombocytopenia, and renal insufficiency. This underscores the need to emphasize that TAFRO syndrome is principally a systemic inflammatory disorder. Timely diagnosis and treatment with dexamethasone, followed by several sessions of lenalidomide and dexamethasone (Rd) regimen chemotherapy, resulted in complete remission (CR), and was followed by autologous stem cell transplantation (ASCT). This case offers valuable insights into the diagnosis and treatment of POEMS syndrome, which may prompt a reconsideration of the diagnostic criteria for this syndrome.