Microangiopathic hemolytic anemia (MAHA) can be observed as a paraneoplastic syndrome (PS) in certain tumors. MAHA-related signet ring cell carcinoma (SRCC) of an unknown origin is very infrequent. Herein we present a SRCC case presented with refractory acquired thrombotic thrombocytopenic purpura (TTP). A 35-year-old man applied to the emergency service with fatigue and headache. His laboratory tests resulted as white blood cell 9,020/mu L, hemoglobin 3.5 g/dL, platelet 18,000/mu L. Schistocytes, micro-spherocytes, and thrombocytopenia were observed in his blood smear. MAHA was present and he was considered as having TTP. Plasma exchange treatment was initiated; however, he was refractory to this treatment. Thorax and abdomen computerized tomography revealed thickening of minor curvature in stomach corpus with hepatogastric and paraceliac lymphadenopathy. Bone marrow (BM) investigation by our clinic resulted as the metastasis of adenocarcinoma. Ulceration and necrosis were observed by gastric endoscopy procedure. Biopsy was taken during endoscopic intervention, which resulted as SRCC. MAHA may be seen as a PS in some tumors, especially gastric cancers. Tumor-related MAHA is generally accompanied by BM metastases. As a result, BM investigation may be used as the main diagnostic method to find the underlying cancer. The clinical course of cases with tumor-related MAHA is usually poor, and these cases are usually refractory to plasma exchange treatment. In conclusion, physicians should suspect a malignancy and BM involvement when faced with a case of refractory TTP.