Splenomegaly is an unusual finding among North Americans, but is commonly seen in many parts of the world. Increasingly, it can be encountered locally among recent immigrant and refugee populations. A broad differential diagnosis is required. We report the case of a 33-year-old refugee with multiple potential causes for splenomegaly. Empiric treatment of one of the infectious contributors to his splenomegaly resulted in a significant improvement of his quality of life, illustrating the importance of a thorough evaluation of potential causes of splenomegaly, especially in refugee and immigrant populations.