A 3-yr-old female bearded dragon (Pogona vitticeps) was presented to the Exotic Pet and Wildlife Veterinary Teaching Hospital at the National Autonomous University of Mexico with a 3-day history of right hindlimb swelling. Radiographs revealed lysis of the right stifle and tarsal bone. Fine-needle aspiration from the stifle revealed large numbers of macrophages and giant cells, and Ziehl-Neelsen stain revealed intracytoplasmic acid-fast bacilli-like bacteria. Standard aerobic culture was performed, with negative results. Pain management was provided with meloxicam (0.2 mg/kg PO q24h) and tramadol (11 mg/kg PO q12h); the owner declined antimicrobial therapy. Three weeks later, radiographs revealed the progression of the lytic lesions to the distal femur, proximal tibia, and tarsal bones. One month later, the patient presented for left hindlimb swelling. Follow-up radiographs revealed a total loss of the right stifle and the tibiotarsal and tarsometatarsal joints, as well as new lytic lesions at the left stifle and tibiotarsal joints. Based on the grave prognosis, the lizard was euthanized. At necropsy, granuloma-like lesions were found at the stifles and the coxofemoral, tibiotarsal, and tarsometatarsal joints. Imprints made from these lesions revealed acid-fast bacilli. No other gross lesions were identified. Microscopic review of the tissues revealed severe granulomatous osteomyelitis and myositis, as well as a severe histiocytic and heterophilic hepatitis with acid-fast intrahistiocytic bacilli. Polymerase chain reaction results confirmed these bacteria as nontuberculous mycobacteria. To the authors' knowledge, this is the first postmortem report of septic arthritis associated with Mycobacterium spp. in a bearded dragon; only two other cases have been reported, both without postmortem findings.