Background: Case Presentation: A HIV-positive patient subsequently developed TM pulmonary infection. Clinical symptoms and laboratory test results were non-specific. Imaging studies revealed pulmonary masses, and the patient was misdiagnosed with lung cancer outside the hospital, leading to an erroneous surgical resection. The patient did not improve postoperatively but instead developed high fever and persistent cough, with symptoms worsening. During treatment at our hospital, the patient was definitively diagnosed with TM lung infection, not lung cancer. Due to the rarity of TM infection and lack of experience, treatment was delayed, leading to worsening of the patient's condition. The patient exhibited gastrointestinal bleeding, progressive neurological dysfunction, hydrocephalus, and multi-organ dysfunction, which ultimately resulted in the death of the patient. Conclusion: TM infections often present with insidious onset, prolonged course, and lack of specific clinical symptoms, imaging findings, or laboratory test characteristics, making diagnosis challenging and frequently leading to misdiagnosis or missed diagnosis, resulting in high mortality rates. Therefore, clinicians should enhance their diagnostic and treatment experience regarding TM infections in HIV-positive individuals or populations in non-endemic regions, initiate pathogen culture and histopathological diagnosis as early as possible, and integrate the results of mNGS and mass spectrometry analysis to improve the detection rate and early diagnosis rate of TM infections. This will ensure that patients can receive timely and accurate treatment, which is crucial for improving their prognosis.