The Medici family ruled Florence for most of the period from the 1430s to the 1730s, with the senior (primogenito) branch predominating until the line ended in the 1530s and the cadet (secondogenito) branch predominating thereafter. Recent studies have identified a familial syndrome consisting of cutaneous symptoms, peripheral arthropathy and spinal ankylosis in the primogenito branch of the family, and the presence of diffuse idiopathic skeletal hyperostosis (DISH) in two members of the secondogenito branch. These findings raise the question of whether DISH was also a component of the primogenito familial syndrome. The present study provides a further specification of the ossification diathesis in the familial syndrome of the primogenito branch of the Medici family. Recently discovered photographs of exhumed Medici skeletons from the primogenito line are examined, with a focus on spinal, sacro-iliac and peripheral ossifications. These observations are supplemented with published reports of radiological, histological and macroscopic studies of the skeletons. Our interpretations of the ossification data relating to the primogenito branch of the Medici family are supportive of a diagnosis of DISH. DISH was one component of the triple pathology identified as a syndrome in the fifteenth century primogenito Medici line. As a diagnosis of DISH has recently been proposed for two sixteenth century members of the secondogenito branch of the family, it appears that the same condition affected both branches of the Medici lineage, without excluding other forms of undifferentiated joint and spondylarthropathies.