We reported a case of two different episodes of critical coagulopathy in a single patient with metastatic prostate cancer (mPC). The patient initially visited the emergency room with a huge left retroperitoneal hematoma, high serum prostate-specific antigen level, and signs of acute disseminated intravenous coagulation (DIC) from mPC. With blood product replacement and anti-androgen therapy, the DIC-related symptoms and signs were relieved. During the follow-up, he was treated with docetaxel chemotherapy for hormone refractory PC. Four years later, he visited the emergency room again with relapsed coagulopathy and severe anemia that were not replaced with blood products. The laboratory findings were consistent with thrombotic thrombocytopenic purpura rather than DIC. A satisfactory recovery was achieved with a new cycle of docetaxel chemotherapy. Differentiation of the coagulopathies in PC is difficult; therefore, we describe the different features of two overlapping coagulopathies, which will be helpful in deciding on urgent treatment.