Disseminated non-tuberculous mycobacterial (NTM) infection can affect patients with underlying immunosuppressive conditions. Despite being rare, delay in diagnosis can lead to life-threatening uncontrolled immune response and hemophagocytic syndrome (HPS). We report a case of a 63-year-old female with suspected autoimmune disease, in whom HPS was diagnosed according to HLH-2004 criteria and H-score. Mycobacterium avium (M. avium) was isolated from blood culture, bronchoalveolar lavage (BAL) and bone marrow biopsy. In immunosuppressed patients, early clinical suspicion and prompt microbiological diagnosis of mycobacterial infection together with drug susceptibility tests (DST)-based treatment, as well as HPS, are pivotal to increase the likelihood of treatment success.