Littoral cell angioma is a recently described vascular tumor of spleen with an unknown etiology. We present a case in a 74-year-old woman with severe anemia, thrombocytopenia and palpable splenomegaly. The computed tomography of abdomen showed well-defined multiple nodules in spleen. Splenectomy was performed and the histological and immunohistochemical features of splenic tumor were consistent with a littoral cell angioma. The patients had persistent anemia and thrombocytopenia after splenectomy. We suggest hepatic destruction or other autoimmune mechanism contributes persistent bicytopenia. This case illustrated the refractory bicytopenia combined with littoral cell angioma.