The present paper reports, to the best of our knowledge for the first time, the efficacy and tolerability of the combination of interferon (IFN)α-2a in pegylated formulation and rituximab after a "priming" phase with IFN in the frontline treatment of hairy cell leukemia (HCL) in a profoundly immunosuppressed patient with a <i>Mycobacterium abscessus</i> infection at onset. The gene discussed is IFNA2; the disease is hairy cell leukemia.