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Adult-onset immunodeficiency (AOID) syndrome due to the presence of anti-interferon gamma antibody (AIGA) is characterized by multiple opportunistic infections. We report a case of a 65-year old healthy woman who suffered from Legionella pneumophila and Mycobacterium intracellulare co-infection with clinical presentation mimicking metastatic lung cancer. She presented with chronic cough and weight loss. Her positron emission tomography scan showed a right upper lobe mass, mediastinal lymphadenopathy and multiple bone lesions. Acid fast bacilli culture of the lung mass and mediastinal lymph node revealed Mycobacterium intracellulare and she improved with prolonged antibiotic. Relapse of disseminated Mycobacterium intracellulare infection occurred 15 months post-treatment and AIGA was positive with functional neutralizing activity on downstream immune pathway. AOID syndrome secondary to AIGA was diagnosed. This case illustrated the importance of high index of suspicion of AOID syndrome and the difficulty of early diagnosis. Further studies on its predictive factors and AIGA-targeted treatment modalities are urgently needed., Competing Interests: None declared., (© 2023 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)