Microangiopathic hemolytic anemia (MAHA) is a well-documented but rare complication of disseminated cancer; it usually occurs in the late or terminal stage of cancer. We describe a case of metastatic carcinoma of unknown origin in which MAHA was the initial presentation. A 36-year-old woman came to our hospital with lower back pain and progressive exertional dyspnea for 8 weeks. Hemolytic anemia, thrombocytopenia, and leukoerythroblastosis were found on admission. The peripheral blood smear revealed polychromasia, poikilocytosis, and many schistocytes. Bone marrow biopsy disclosed metastatic carcinoma. After careful workup, we failed to find the primary site of cancer. The anemia and thrombocytopenia responded dramatically to combination chemotherapy with 5-fluorouracil, mitomycin C, and cisplatin. This case indicates that metastatic carcinoma should be included in the differential diagnosis in previously healthy patients with MAHA.