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The Monito del Monte is the only extant member of its family (Microbiotheriidae) and the only surviving member of an ancient order, the Microbiotheria. The oldest microbiothere currently recognised is Khasia cordillerensis, based on fossil teeth from Early Palaeocene deposits at Tiupampa, Bolivia. Numerous genera are known from various Palaeogene and Neogene fossil sites in South America. A number of possible microbiotheres, again represented by isolated teeth, have also been recovered from the Middle Eocene La Meseta Formation of Seymoour Island, Western Antarctica. Finally, several undescribed microbiotheres have been reported from the Early Eocene Tingamarra Local Fauna in Northeastern Australia; if this is indeed the case, then these Australian fossils have important implications for our understanding of marsupial evolution and biogeography.

Although once thought to be members of the order Didelphimorphia (the order that contains the Virginia Opossum), an accumulation of both anatomical and genetic evidence in recent years has led to the conclusion that microbiotheres are not didelphids at all, but are instead most closely related to the Australasian marsupials; together, the microbiotheres and the Australian orders form the clade Australidelphia. The distant ancestors of the Monito del Monte, it is thought, either remained in what is now South America while others entered Antarctica and eventually Australia during the time when all three continents were joined as part of Gondwana, or else were part of the Australian marsupial fauna which reinvaded South America.

• Mikko's Phylogeny Archive
• Entry by the Zoological Society of London