A 59 year-old man presented with a history of intermittent and disabling pain in his left knee for 2 years. There were no other complaints such as fever, weight loss, or coughing. He had undergone arthroscopy a year earlier to treat osteoarthritis. A second arthroscopy was performed with synovial tissue biopsy in July 2010; microbiological analysis revealed the presence of M. tuberculosis and acid-fast bacilli (AFB). Antibiogram showed a normal sensitivity pattern. Histopathological assessment revealed granuloma with caseous necrosis, suggesting tuberculosis. Chest radiography revealed bilateral diffuse pulmonary infiltrates with a micronodular pattern. Immunological examination for the human immunodeficiency virus (HIV) was negative. The patient began receiving treatment with anti-tuberculosis drugs as part of a regimen, including rifampicin, isoniazid, pyrazinamide, and ethambutol. Pain symptoms initially improved. However, 2 months after starting the treatment, he started experiencing pain and swelling, and developed a fistula in the contralateral knee. Magnetic resonance imaging (MRI) showed signs of osteomyelitis in the right femur and tibia (Fig. 1), and surgical drainage with bone biopsy suggested tuberculosis. However, there was no microbiological growth in mycobacteria-selective culture medium. After 6 months of treatment, the patient presented with a fistula in his left knee, which was positive for AFB. M. tuberculosis was isolated from a selective medium in a reference laboratory. However, sensitivity tests could not be performed. Once again, immunological assessment and real-time PCR results were negative for HIV. Immunoglobulin values were normal. His therapeutic regimen was subsequently extended. In the eighth month of treatment, the fistula was still observed in his right knee, and the collected material revealed the presence of AFB. MRI revealed the presence of periarticular collection. One year after the initiation of isoniazid/rifampicin treatment, there were no fistulas and findings of MRI suggested improvement. In August 2012, after 24 months of isoniazid/rifampicin treatment, the patient returned to the outpatient clinic presenting with a new fistula in his right knee. MRI revealed periarticular and intraosseous collection in the left femur as well as a large collection in the right calf. Surgical drainage of a large volume of purulent material was performed, and the contents were sent to 3 laboratories; M. tuberculosis was not isolated in any of the laboratories, but the results of tests conducted in 2 laboratories indicated that the material was positive for AFB and M. tuberculosis was detected by real-time PCR. By February 2013, the patient had been treated with isoniazid/rifampicin for 30 months and he began to experience clinical improvement with the disappearance of the fistulas. The final MRI scan showed improvement of osteomyelitis signs. The treatment was discontinued in January 2013, and the patient is currently in clinical follow-up.