A 31-year-old man presented to our outpatient clinic with redness, swelling, and severe pain in both knees as well as an inability to walk since one year ago. The patient who has been HIV positive for 7 years had a history of severe prurigo nodularis for four years and had tubercle bacillus bloodstream infection two years ago. His antiretroviral treatment was successful. He did not have any relevant family history or history of genetic diseases. After admission, the patient underwent bilateral curettage for tibial osteomyelitis under epidural anesthesia. An anterior incision was made at the proximal end of the tibia. Bone destruction was observed at up to a depth of approximately 2 cm inside the tibial tubercle, and a large amount of purulent secretion was discharged from the anterior tibial incision. The inflammatory granulation tissue and scar tissue were removed. A small curette was used to eliminate the inflammatory granulation tissues and pus in the remaining dead space, and the removed material was placed in a sterile bag. Bone cement was used to fill in the tibial defect, and the wound surface was covered with VSD dressing and fixed on the peripheral skin. Continuous vacuum aspiration was performed to drain the wound (Figure 1). Culture of the wound drainage fluid showed no growth of mycobacteria or other bacteria after 1 week, but a small number of red acid-fast positive spheroids were detected on smear microscopy (Figure 2). Considering that the patient had a history of tuberculous bloodstream infection and had symptoms of low fever and fatigue, we initially suspected a diagnosis of tuberculous osteomyelitis. The patient was immediately administered anti- multidrug-resistant tuberculosis (MDR-TB) treatment, but the response was not good. After 21 days of culture, no M. tuberculosis growth was observed, and the Xpert MTB/RIF and T-SPOT.TB tests were negative, indicating that there was no TB infection and explaining the patient's lack of response to the anti-MDR-TB treatment. As some red acid-fast spheroids had been observed on microscopy, we now considered the possibility of infection with the L-forms of M. tuberculosis or NTM. Culture, microscopic examination, electron microscopy (Figure 3), polymerase chain reaction (PCR) assays and a reversion test (Figure 4) confirmed the presence of NTM and its L-forms. The patient was therefore treated with moxifloxacin, protionamide, linezolid, isoniazid, rifampicin, and ethambutol for 10 months, according to the results of the drug-sensitivity test. After this treatment, the wounds appeared clean, with no evidence of redness, swelling, heat, or pain. Thus, amputation of the affected legs was avoided.