Few recent reports have indicated that Mycobacterium massiliense causes various infections including respiratory infection. However, there is scarce information on the clinical significance, natural history of the infection, and therapeutic strategy. This report describes a case of an immunocompetent old man infected by M. massiliense that causes acute respiratory failure. In light of the general courses of non-tuberculous mycobacterium infections, rapid progression and fatality are very rare and odd. In addition, we discuss the biological and pathological properties of M. massiliense with the review of cases reported previously including our fatal one.