BackgroundPleural involvement by non-tuberculous mycobacteria (NTM), especially NTM empyema in the immunocompetent patient without pulmonary diseases is a rare disease. It is difficult to diagnose with only a few cases of immunodeficient patients in the literature.Case presentationWe describe a 63-year-old male with empyema due to NTM and highlight the challenges of diagnosis.ConclusionsNon-tuberculous mycobacterial infection should be considered as a cause of pleuritis or empyema without pulmonary disease, however it is a real diagnostic dilemma.