POEMS syndrome is a multisystem disorder caused by a neoplasm of plasma cells. The acronym "POEMS" refers to some of its characteristics: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. It's a rare condition, and available information has been presented as case series. Its exact incidence is unknown. The pathophysiology is not yet fully clear, but the role of proinflammatory cytokines and overproduction of vascular endothelial growth factor is recognized. Diagnosis is based on criteria defined by the International Myeloma Working Group. However, atypical cases that do not meet all the criteria have been described, in which observation is chosen until symptoms appear or empirical treatment is initiated based on symptomatic involvement. We describe a series of 2 cases of patients with POEMS syndrome studied and treated at Carlos Van Buren Hospital in Valparaíso, Chile. Both meet the criteria for diagnosis but with variable presentations due to different elements of the minor criteria. Large retrospective series report polyneuropathy as the most common finding. Additionally, they have monoclonal gammopathy of undetermined significance (GMSI). Both patients underwent the same therapy regimen with melphalan/dexamethasone. Nowadays, both patients are stable and undergoing outpatient monitoring.