Three acaremyid rodents from the Miocene of Patagonia are described. Galileomys antelucanus, gen. et sp. nov. (Colhuehuapian SALMA, early Miocene) is the most plesiomorphic genus within the Acaremyidae. Galileomys? colloncurensis, sp. nov. is the first acaremyid recorded from the Colloncuran SALMA (middle Miocene). The generic referral is tentative because the known material does not display enough characters. Acaremys cf. murinus Ameghino, 1887 represents a second Colhuehuapian acaremyid. Cladistic analyses of dental and mandibular characters do not support previous hypotheses that Sciamys and Acaremys are the ancestors of the Octodontidae. On the contrary, these two genera and Galileomys constitute a monophyletic group united by the presence of a hypoflexus in P4, a well defined anterodorsal limit of mandibular masseteric fossa, and a figure-eight-shaped molar pattern. The inclusion of other genera in the Acaremyidae is not supported by cladistic analysis. A shared figure-eight-shaped dental pattern was the primary basis for a presumed close relationship between the Acaremyidae and Octodontidae, but this state evolved independently in the two taxa. The Acaremyidae is an extinct, early radiation of the Octodontoidea that persisted at least until the middle Miocene. The Octodontidae probably originated from an ancestor closer to the “echimyids” than to the Acaremyidae, with neither normal dental replacement nor mental foramen.