Myelodysplastic syndromes (MDS) are an heterogeneous group of clonal hematopoietic disorders characterized by dysplasia, bone marrow (BM) failure and an increased risk of acute myeloid leukemia (AML).1 Human immunodeficiency virus (HIV) infection is a chronic disease requiring lifelong treatment with combination antiretroviral therapy (ART). Thanks to ART, HIV infected patients live longer, with life expectancies similar to non-HIV patients. However, patients with well controlled HIV infection have increased rates of non-AIDS associated diseases such as cancer, neurocognitive impairment and cardiovascular disease (CVD).2 Chronic immune activation in HIV patients on ART, secondary viral co-infection as well as lifestyle factors are thought to be responsible for increased cancer burden in this population. Although people living with HIV are at increased risk of hematological malignancies (non-Hodgkin and Hodgkin lymphoma), the risk of MDS is not well established.2 Less than 50 cases of MDS in HIV patients have been reported in literature as case reports or case series.3 Therefore, management strategies are widely undefined. We present 2 patients with MDS in the setting of well controlled HIV infection. We discuss diagnostic challenges, treatment with azacytidine and lenalidomide in this setting and the pathophysiology of HIV in MDS development.