The chronic diffuse sclerosing osteomyelitis (CDSO) of the mandible has been described as an inflammatory disease characterized by recurrent episodes of intense pain in the mandible, often accompanied by trismus, paresthesia and progressive mandibular deformity. The etiopathogeny of this entity is not fully known. The differential diagnosis must be carried out very carefully, and the treatment results are very disappointing. Recently, evidence that suggests that CDSO may be the mandibular location of a more diffuse condition, the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome, has been offered. We describe two clinical cases of CDSO of typical evolution which fulfill the criteria for SAPHO syndrome, offering us an occasion for a review of the current literature.