Discriminating between indolent small intestinal CD4+ T-cell lymphoma and secondary GI involvement by certain subtypes of PTCL, especially angioimmunoblastic T-cell lymphoma, HTLV1-associated adult T-cell leukemia/lymphoma, mycosis fungoides and T-cell prolymphocytic leukemia/lymphoma, can be challenging on morphologic and phenotypic grounds. The gene discussed is CD4; the disease is T-cell prolymphocytic leukemia.