Hemophagocytic lymphohistiocytosis (HLH) associated with visceral leishmaniasis (VL) is a very rare phenomenon. We report the first known North American case in a 21 month old boy. He was initially diagnosed with Epstein Barr virus (EBV) triggered HLH and treated with the international treatment protocol, HLH-2004. Stem cell transplant was planned due to repeated reactivations of disease, but his pretransplant bone marrow revealed an unexpected protozoan-Leishmania donovani. Treatment with liposomal amphotericin B led to resolution of all manifestations of HLH. We discuss how the clinical and laboratory features of both entities can closely mimic each other and are extremely difficult to differentiate. This case also raises the question of whether to screen all children with suspected HLH for Leishmania in a non endemic area.