Ancestral therian mammals evolved a number of modifications of their skeletal systems.

Modern placental and marsupial mammals are classified as therians because they give live girth to their young. Kuehneotherium had dental characteristics (such as molar occlusion patterns) of therian mammals. A few species in the Cretaceous seem to predate the split between marsupials and placentals such as Deltatherium (tooth formula 4?,1,3,3-4/1-2,1,3,4-3) and Kielantherium. Some extinct groups left no descendants.

In therian mammals, the occipital condyles were positioned higher on the skull and the maxillary and mandibular branches of the trigeminal pass through alisphenoid (through the foramen rotundum and foramen ovale) as opposed to between alisphenoid and petrosal. The ectopterygoid was no longer part of the palate, the alisphenoid was expanded, and, after protoeutherians, a groove existed in the sphenoid for the promontory artery. The angular process of the dentary was more developed. In primitive therian mammals, the cusps on cheek teeth were triangular but no longer linear. Tribosphenic molars had evolved by the Early Cretaceous whose features included a talonid basin and a protocone.
Cervical ribs fused to the centrum in early mammals. These ribs were not fused in the most primitive mammals nor are they fused in modern montremes, although they had fused in some advanced cynodonts. Because the transverse processes of cervical and lumbar vertebrae are actually composed of ancestral transverse processes plus vestiges of ribs, they are referred to as pleurapophyses. The early mammals lost the proatlas and the zygapophyses between the altas and axis, allowing for free rotation between the first two vertebrae. In the protoeutherian Asioryctes, the intercentrum of the atlas had not yet fused.
Therian mammals evolved a spine of the scapula which is actually homologous to anterior border of monotreme and cynodont scapula. The supraspinous fossa is a new structure which exists only in therian mammals. The glenoid cavity became more open, increasing importance of rotator cuff muscles for the stabilization of the shoulder. The interclavicle was lost.