Introduction: chronic non-bacterial osteomyelitis (CNO) is a non-infectious inflammatory of unknown etiology. Case description: ABA, female, 16 years old, was admitted with a pain in her left thigh. At the time, it was suspected to be caused by a tumor, and a bone scintigraphy was requested, which evidenced a focal area of increased uptake in the distal metadiaphyseal area of the left femur. A bone biopsy was performed, and its result was compatible with chronic osteomyelitis. The patient started taking pamidronate (withdrawn due to treatment failure) and methotrexate (subsequently suspended due to urticarial reaction). After some years of clinical stability, a new focal area of osteomyelitis appeared, in the distal right femur. The use of anti-TNF (infliximab) was chosen, resulting in an improvement of the algic state. Discussion: the diagnosis of CNO is made by process of elimination and is based on clinical, laboratorial, radiological, bacteriological and histological data. Non-hormonal anti-inflammatory and bisphosphonate drugs are recommended as initial therapy. Disease-modifying drugs, steroids and anti-TNFα have been used in severe and recurring cases. Conclusion: the authors present a CNO case with good response to anti-TNFα after treatment failure with bisphosphonates.