The POEMS syndrome is a rare and multisystemic disease characterized by the presence of polyneuropathy, organomegaly, endocrinopathy, presence of M protein, and alterations in the skin. The existence of bone lesions is frequent, being generally blastic or mixed and rarely lytic. We present the case of a 54-year-old male patient diagnosed with POEMS syndrome, with atypical presence of lytic lesions, who was referred for an 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) study for initial staging of the process. There were several hypermetabolic foci coinciding with bone lesions, reaching a maximum standardized uptake value of 15 at the level of the right iliac bone with associated soft-tissue mass. PET-CT is an adequate tool for evaluation, diagnosis, and monitoring of the pathology. The scan allows the detection and selection for its biopsy of bone lesions and lymphadenopathies.