Abstract Introduction Atypical mycobacteria are environmental organisms that cause opportunistic infections in humans. Case report A 50-year-old electronics engineer sought advice about starting TNFα antagonist therapy for ankylosing spondylitis. Disease duration was 23 years and current treatment was methylprednisolone 4 mg/d. Atypical skin lesions and knee arthritis were noted. Fluid aspirated from the knee showed inflammatory properties and a few acid-fast bacteria, which a line probe assay identified as Mycobacterium chelonae. The same organism was found in a skin biopsy from a thigh lesion. Antimicrobial treatment was started immediately. Inadequate results 6 months later prompted synovectomy of the knee followed by interferon gamma, 50 μg/m 2 body surface area subcutaneously 3 times a week. After 16 months, there were no new skin or joint lesions, and the antimicrobials and interferon gamma were therefore discontinued. Conclusion This highly unusual case suggests that interferon gamma may be effective in patients with M. chelonae infection that fails to respond adequately to antimicrobials.