The Central Andes of Peru and Ecuador have seen periods of language shift and language replacement in which expansive languages superseded earlier layers of local languages, as has happened numerous times in other regions around the world. In colonial times, members of the expansive Quechua family still coexisted with a number of local languages, and it is almost certain that Quechua had replaced several such languages in prehistory. In this paper, I focus on the Quechua variety spoken in the southern Ecuadorian highlands of Cañar and Azuay, and ask what can be learnt of the replaced language(s), and thereby the linguistic prehistory of the Southern Ecuadorian highlands, from its lexicon. By employing criteria developed elsewhere, I identify possible substrate items in the lexicon, highlighting philological points and linguistic analysis during the discussion. I further explore what these items suggest for the hypothesis – suggested in passing but not yet fully explored – that the original language of the region was a southern representative of the Barbacoan family of languages. I conclude that they provide some support for the hypothesis, but that the evidence is ultimately equivocal. [ABSTRACT FROM AUTHOR]