We report a case of atypical muscle localization of plasma cell leukemia (PCL), arisen from a secondary leukemic transformation of multiple myeloma (MM), detected by F-18 FDG PET/CT. A 57-year-old woman with a history of MM received chemotherapy and hematopoietic stem cell transplantation with complete treatment response. Five years later, the patient presented a recurrence of MM and an evolution in PCL. F-18 FDG PET/CT showed areas of increased radiopharmaceutical uptake in some muscles of the right leg and right thigh, corresponding to muscle localization of PCL, therefore allowing adequate treatment planning.