Introduction: Tubercular tenosynovitis of the wrist and hand, although rare, presents a diagnostic dilemma primarily due to its non-specific clinical presentation, insidious course, and the large number of differentials that mimic it. When the diagnosis is late or delayed, significant bone and tendon complications occur. Large progressive swelling around the wrist in TB endemic countries should raise an early suspicion of being of tubercular etiology and should be high on the list of differential diagnoses. Case Report: A 48-year-old female presented with a large progressive swelling on the volar aspect of the left wrist and palm for 7 months, associated with increasing pain, stiffness, limited wrist range of movements, and weakened grip strength. Magnetic resonance imaging (MRI) revealed synovitis and fluid within flexor tendon synovial sheaths. The patient underwent an excision of the mass in toto and the cut section revealed an irregularly thickened wall with rice bodies within. Histopathological examination was indicative of a large ganglion cyst. GeneXpert MTB/RIF assay detected Mycobacterium tuberculosis. Despite histopathology being inconclusive, a diagnosis of TTS was considered due to the patient’s clinical presentation, MRI, and operative findings. The patient was started on an antitubercular drug regimen for a 1-year duration. The patient regained a complete range of movements of fingers and wrist and normal grip strength at the 3rd month follow-up. Conclusion: TTS is a challenging diagnosis entity. The diagnostic confirmation was achieved either by histopathology or detection of the organism either by culture or GeneXpert MTB/RIF assay. When the diagnosis is unsupported, drug therapy can be initiated empirically on strong suspicion of tuberculosis, especially in TB endemic areas.