Littoral cell angioma (LCA), a primary vascular neoplasm originating from splenic red pulp littoral cells, was initially thought to be an extremely rare pathology. There have been an increasing number of cases reported in the literature. However, the etiology and prevalence of LCA is still unclear, partly due to the rarity of cases. The association of LCA with internal organ cancers, specifically lymphoma, has also been reported. In the patients with a history of cancer/lymphoma, the accurate diagnosis of LCA as the cause of the splenomegaly is challenging. Here we present a case of LCA in a patient with non-Hodgkin B-cell lymphoma and alpha-thalassemia trait. To our knowledge, this is the first report of the coexistence of LCA and thalassemia and only the second report of LCA and marginal-zone non-Hodgkin B-cell lymphoma. We review the literature and discuss the radiologic and pathologic findings of this case compared with the previously reported cases.