POEMS syndrome (polyneuropathy, organomegaly, M-protein, and skin changes) is a rare plasma cell disease with small tumour mass and multisystem involvement. Since 2003 POEMS syndrome has been a nosological entity with approved diagnostic criteria, though its etiology and pathogenesis are still not clear. Males are more often affected, with peak incidence in the 5th and 6th decades. The major diagnostic problems are difficult detection of plasma cell infiltration in the osteosclerotic lesions and M-gradient most often low concentration IgA (lamda). We present a case of POEMS syndrome in a 47-year-old male patient who initially presented with edema of the lower limbs, moderate lymphadenopathy, hepatosplenomegaly, histological findings of Castleman disease with marked sinusoidal angioproliferation in the lymph nodes and multiple osteosclerotic lesions. Pleural effusion, ascitis, renal failure, progressive lower limbs polyneuropathy with invalidisation of the patient developed later. The attempts to detect lymphoproliferative process by myelogram, trephine biopsy, histological examination of lymph node and the spleen were ineffective and deceptively non-informative, neither did immunoelectrophoresis reveal M-grade. Diagnosis was made after bone biopsy of the largest osteosclerotic lesion and immunofixation (monoclonal IgA, lamda in the serum). The patient underwent treatment with alkylating agents and corticosteroids, radiation of the predominant osteosclerotic lesions and therapy with radioactive strontium. The general condition improved, lymphadenomegaly, skin lesions, pleural effusion and ascitis regressed and renal function was restored. There was a minor improvement of the neurological symptoms. Autollogous stem-cell transplantation is also recommended in literature for patients with generalized bone lesions or progressive and disease-resistant therapy.