Placental mammals (Placentalia) are a very successful group that, today, comprise 94% of all mammalian species. Recent phylogenetic analyses, coupled with new, quite complete fossils, suggest that the crown orders were all established rapidly from a common ancestor just after the Cretaceous/Tertiary (K/T) boundary 65 million years ago. Extensive molecular and morphologic evidence has led to a description of the common ancestor of all Placentalia in which a two-horned uterus and a hemochorial placenta are present. Thus, the process of placentation in which the placenta invades and anchors to the uterine epithelium was already established. One factor that has been suggested as a crucial component of this process is placenta-specific protein 1 (PLAC1). A phylogenetic analysis of the PLAC1 protein in 25 placental mammal species, representing nine of the sixteen crown orders of the Placentalia, suggests that this protein was present in the placental common ancestor in the form we see it today, that it evolved in the Placentalia and has been subject to the effects of purifying selection since its appearance.