Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare disorder of unknown aetiology with neonatal onset, characterized by severe arthropathy, persistent skin rash and central nervous system disease. Joint involvement may vary from minimal swelling to destructive arthritis, with inability to stand or walk. The most striking findings of CINCA syndrome are cartilage anomalies with epiphyseal modifications and abnormal ossification, for which a pathogenetic role of tumour necrosis factor‐α (TNF‐α) is postulated. We describe a 4‐year‐old child affected with CINCA syndrome and presenting progressive joint disease, in whom non‐steroidal anti‐inflammatory drugs (NSAID) and systemic corticosteroidal therapy had been ineffective. Etanercept, anti‐TNF‐α therapy, was administered over a 6‐month‐period resulting in a dramatic improvement of the arthropathy. This good response to anti‐cytokine treatment supports our hypothesis that TNF‐α might play an important role in the pathogenesis of CINCA syndrome, which needs to be evaluated and confirmed in further studies.