We describe four unrelated children with neonatal maculopapular rash, fever, arthritis, hepatosplenomegaly, lymphadenopathy, eye involvement, and neurologic symptoms. Radiographs of the joints were surprisingly similar, showing an abnormal epiphyseal and metaphyseal appearance. These clinical and radiologic findings allowed us to include these children in a very peculiar syndrome described as infantile-onset multisystemic inflammatory disease. A chondrosarcoma developed in one of our patients.