Abstract : Chronic granulomatous disease [CGD] is a rare congenital defect of phagocyte function characterized originally by chronic suppurative lymphadenitis, hepatosplenomegaly, pulmonary infiltrates, and eczematoid dermatitis. Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of lymphocyte homeostasis, characterized by persistence of autoreactive cells (double-negative TCR αβ cells) that often manifest with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Unfortunately, some of these features are also involved in other conditions, such as Chronic Granulomatous Disease, which can confound the diagnosis. This report describes a 4-year-old girl with chronic hepathosplenomegaly, thrombocytopenia, recurrent respiratory infection, elevated double-negative TCR αβ cells and hypergammaglobulinemia. These criterias misdiagnosed as ALPS and planned to be treated with corticosteroids and immunosuppressive drugs, but the genetic evaluation revealed a mutation in NCF2 leading to CGD. This observation should alert pediatricians to pay extreme attention and include CGD in the differential diagnosis of a child with hepathosplenomegaly, cytopenias, and recurrent infections, obtain discriminating screening laboratory assays, such as Nitroblue tetrazolium test (NBT), and Dihydrorhodamine (DHR) flow cytometry assay.