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Background: Tuberculosis (TB) is a potentially life-threatening disease that primarily affects the lungs. Mycobacterium tuberculosis (M. tuberculosis) can also infect other body sites like the pleura, kidney, and skin, causing extrapulmonary tuberculosis (EPTB). The number of EPTB deaths can be reduced significantly if rapid and effective technologies such as Xpert Ultra are implemented for early diagnosis of this fatal disease. This study aimed to validate the GeneXpert utilising non-respiratory specimens for early EPTB detection at Lesotho's National Tuberculosis Reference Laboratory (NTRL). Methods: Although this was primarily an experimental study, it did incorporate data from the NTRL database. A variety of extrapulmonary clinical specimens were tested using the GeneXpert (index test) and culture (gold standard) for the presence of M. tuberculosis. All ages and sex were included. IBM Statistical Package for the Social Sciences (SPSS) version 26 was used for statistical analysis. Results: From 2016 to 2019, a total of 176 specimens were tested for EPTB. Pleural fluid was the most routinely obtained specimen type, representing 39.2%, followed by 14.2% ascitic fluid, and 13.6% cerebrospinal fluid (CSF). From the specimens analysed, 34 were positive for EPTB and were detected using both GeneXpert and culture techniques. The GeneXpert's overall sensitivity was 92.3% and specificity was 87.1%. Conclusion: Results from this study suggest that the GeneXpert can be trusted as a critical tool for the early detection of various forms of EPTB and early treatment initiation. The GeneXpert can be successfully used as an adjunct diagnostic tool at the NTRL in Lesotho. [ABSTRACT FROM AUTHOR]