A 76-year-old man with symptomatic bone metastases from castration-resistant prostate cancer underwent Radium-223-dichloride (Ra-223) therapy. Before Ra-223 therapy, he had normal peripheral blood cell counts. Ra-223 therapy relieved his shoulder and low back pain. The elevation of the serum prostate-specific antigen (PSA), doubling every month during Ra-223 therapy, suggested a PSA flare or relapse. Some lesions showed decrease and some lesions showed increase on Tc-99m hydroxymethylene diphosphonate bone scintigraphy at two weeks after the third injection of Ra-223 therapy. Ra-223 therapy was discontinued due to thrombocytopenia that was getting worse rapidly. After treatment discontinuation, namely four weeks after the third injection of Ra-223, F-18 fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/CT and a biopsy were performed to evaluate for metastases, and bone marrow metastases were found. Ra-223 was effective for osteoblastic lesions, but not for bone marrow metastases. FDG PET/CT, but not a Tc-99m based bone scan, detected diffuse bone marrow involvement by cancer. This case report is the first to clarify the utility of FDG PET for the detection of bone marrow metastases confirmed by pathological examination in Ra-223 therapy for progressive castration-resistant prostate cancer.