Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic microangiopathy. Although most cases are held to be idiopathic, its association with malignancy is well recognized and it usually occurs at the terminal stage of cancer. Bone marrow necrosis (BMN) is another rare disorder defined pathologically as the necrosis of myeloid tissue and medullary stroma with preservation of bone. While hematologic malignancy is the most common underlying disease associated with BMN, it can also be caused by solid tumors. Neither TTP nor BMN associated with colon cancer has been reported. We describe here a patient with the rare association of TTP and BMN displayed as the first manifestation of an advanced colon cancer. The anemia and thrombocytopenia responded not to plasma exchange but to the combination chemotherapy. This case indicates that metastatic cancer should be included in the differential diagnosis of TTP and BMN, and that the chemotherapy may improve the detrimental clinical course.