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Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathy characterized by mechanical hemolytic anemia, thrombocytopenia, and multiorgan dysfunction, resulting from a severe deficiency of ADAMTS13. Among its rare forms, paraneoplastic TTP remains poorly described. We report here the case of a patient in the intensive care unit presenting with paraneoplastic TTP associated with metastatic prostate cancer. This case illustrates the diagnostic challenge posed by the interplay of multiple mechanisms and allows discussion of the different therapeutic options according to the type of TTP, including the role of plasma exchange in paraneoplastic TTP.