The velo-cardio-facial syndrome is one of the most common syndromes of clefting. Previous reports have shown vertical pedigree transmission, but in all cases the gene was maternally transmitted. The genetics of this syndrome had been suspected as autosomal dominant, but X-linked dominant inheritance could not be ruled out. This report describes an instance of male-to-male transmission of the velo-cardio-facial syndrome. In addition, the clinical findings in 60 cases are reported to further delineate the phenotypic spectrum of the syndrome.