We report on two patients with Ph+ chronic myeloid leukemia (CML) in chronic phase who developed severe thrombocytopenia during treatment with interferon-alpha 2A (IFN-alpha 2A). In both cases, we detected the presence of platelet-associated antibodies (PAIg) by autoimmune flow cytometry. We postulated an immune mediated platelet destruction mechanism; corticosteroid therapy was employed and interferon therapy was withdrawn, resulting in an increase in platelet count and a reduction of PAIg. Our observation reports the detection of PAIg associated with IFN-alpha 2A therapy in CML and suggests that this immunomodulant drug could induce thrombocytopenia through a mechanism other than antiproliferation.