[2] It has been hypothesized that Mixean speakers were present, and perhaps represented ruling classes, at the preclassic sites of Kaminaljuyu, Takalik Abaj, and Izapa.

Both of these claims have been criticized: Michael D. Coe and David Stuart argue that the surviving corpus of the few known examples of Isthmian inscriptions is insufficient to securely ground any proposed decipherment.

Their attempt to apply Kaufman's and Justeson's decipherments to other extant Isthmian material failed to produce any meaningful results.

Wichmann (1995) criticizes certain proposed Mixe–Zoquean loans into other Mesoamerican languages as being only Zoquean, not Mixean, which would put the period of borrowing much later than the Proto-Mixe–Zoquean time-frame in which the Olmec culture was at its height.

[8] At the end of the last century, Lyle Campbell dismissed most earlier comparisons as methodologically flawed, but considered the Macro-Mayan proposal the most promising, but yet unproven hypothesis.

[13][14][15] The phoneme inventory of Proto-Mixe–Zoquean as reconstructed by Wichmann (1995) can be seen to be relatively simple, but many of the modern languages have been innovative; some have become quite vowel rich, and some also have introduced a fortis–lenis contrast in the stop series.

Mixe–Zoquean languages are characterized by complex syllabic nuclei made up of combinations of vowels together with the glottal stop and /h/ in the proto-language.