The Acoculco Caldera Complex (ACC), located in eastern Mexico, began its activity during the Pleistocene ~ 2.7 Ma. One of the most relevant and largest rhyolitic eruption in the complex, the Piedras Encimadas Ignimbrite (PEI), occurred during the late post-caldera phase at ~ 1.2 Ma. This ignimbrite is unique with respect to the other caldera products and other contemporaneous ignimbrites in the Trans-Mexican Volcanic Belt (TMVB) because of its ultra-high crystallinity and the absence of pumice fragments. The PEI is made almost entirely of crystals where the main constituents are k-feldspars and silica polymorphs that range from ≤ 5 µm to tens of centimeters in size. XRD on bulk rock, geochemical modeling, FTIR, Raman, and EPMA analyses were carried out in all mineral phases to assess the origin and the causes of high crystallinity within the PEI. We interpret the high crystallinity on the basis of magmatic crystallization of a magma body that was remobilized and altered by post-depositional hydrothermal alteration processes. We suggest that ACC rhyolites are geochemically influenced by at least one crystal mush established during the Pleistocene. We suggest that the PEI could be the result of an erupted crystal mush (melt + crystals), or a cumulate, or an ancient and crystallized reservoir generated after the first ACC collapse due to intrusion or underplating of mafic hot magmas. Extensional episodes within the ACC facilitated the ascent of mafic magmas. This interaction increased the liquid fraction of the mush through partial melting/crystal dissolution, generating a drop in density and viscosity in the mush, thus triggering eruption. The PEI provides evidences for an association between the geochemically-diverse ACC rhyolites with the complex interaction between mafic transitional alkaline magmas and a crustal mush system, promoted by continuous changes in the stress field during the Pleistocene.