Nontuberculous mycobacteria (NTM) may cause pulmonary and extra-pulmonary disease in both immunocompetent and immunocompromised patients. Pleuritis is an uncommon manifestation on NTM disease, and pleuritis caused by Mycobacterium xenopi has only been described once before. Because it is considered to be an environmental contaminant, isolation of M. xenopi from bronchopulmonary secretions or other sites is often dismissed. The disease caused by M. xenopi is usually a pulmonary infection and typically occurs in severely immunocompromised individuals or in immunocompetent patients with an underlying chronic lung disease. We describe an unusual case of pleuritis caused by M. xenopi in a patient without an underlying chronic lung disease and with no evidence of a concurrent M. xenopi pulmonary infection.