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Radium-223 dichloride (Ra-223) is an alpha-emitting radioisotope that targets osteoblastic metastasis of prostate cancer. For Ra-223, a favorable safety profile has been described. However, here we report a case of a fatal hematologic toxicity following the administration of Ra-223 observed at our hospital. An 80-year-old man with castration-resistant prostate cancer (CRPC) and multiple metastatic bone lesions was treated with Ra-223. He was complicated with systemic edema, constipation, and decline of renal function. One week later, he developed pancytopenia which deteriorated gradually, and died with severe prolonged pancytopenia and pneumonia 4 weeks after administration of Ra-223. Our report demonstrates the risk of fatal hematologic toxicity of Ra-223 even though pretreatment clinical and laboratory findings fulfill the selection criteria. Caution should be paid when prescribing Ra-223 to a patient with systemic edema, constipation, and decline of renal function.