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Ureaplasma urealyticum has high nutritional requirements for culture, and it requires special tools for identification. Theoretically, metagenomic next generation sequencing (mNGS) can be used to detect many pathogens in clinical specimens, especially for complex infectious diseases with rare and atypical causes. Here, our patient developed severe pneumonia caused by U. urealyticum infection after allogeneic hematopoietic stem cell transplantation, and the etiology is unclear. After continuous negative culture, U. urealyticum was detected in the bronchoalveolar lavage fluid by mNGS, and azithromycin was used. Because of the difficulty in its diagnosis, diagnosis and treatment of extragenital U. urealyticum infection is challenging. In addition, many broad-spectrum antibiotics are ineffective against this pathogen because it lacks a cell wall. Therefore, early diagnosis and treatment are key to preventing further complications and deaths.