This report describes the case of a young Romanian patient who developed a severe exacerbation of pulmonary tuberculosis during interferon-alpha treatment for chronic hepatitis D. While this occurrence underscores that clinical guidelines should be applied with caution in immigrants from underdeveloped countries, due to the possible presence of unrecognized or unreported comorbidity, the mechanisms for an interferon-related exacerbation of pulmonary tuberculosis are also examined. We propose that IFN-induced weight loss and anorexia may have played an important role in promoting clinical manifestations of tuberculosis in our patient.