Ecandrewsite (ZnTiO3) and other ilmenite-group minerals have been found in amphibolites of the Sierras de Córdoba basement, Argentina, in an area where zinc is a relatively widespread element in the associated metasedimentary and metaigneous sequences. Ilmenite group minerals occur as anhedral to subhedral, tens to a hundred micrometer-sized relic inclusions in titanite. Electron microprobe analyses reveal compositions along a discontinuous solid-solution trend ranging from manganoan ferroan ecandrewsite toward ilmenite s.s., passing through intermediate members such as ferroan manganoan ecandrewsite, zincian manganoan ilmenite, and manganoan ilmenite. Considering that thermodynamic constraints do exist for the solubility of ZnTiO3 in ilmenite under mid- to high-grade regional metamorphic conditions, we believe that ecandrewsite and Zn-rich ilmenite compositions were attained by metasomatic fluid–mineral reactions during retrograde regional metamorphism, i.e., after the centripetal replacement of protolithic Zn-bearing ilmenite group species by titanite. The original composition of the ilmenite group species might have been Zn-poor ilmenite; however, the attainment of ecandrewsite compositions possibly needed an external supply of zinc provided by the fluid. The variations of the zinc contents were controlled by the substitution of Fe by Zn + Mn in the absence of any type of regular zonation. This is the first worldwide report of ecandrewsite in amphibolites, which has so far been described in quartz-rich metasediments, quartz-gahnite exhalites, kyanitic schists, nepheline syenites, metamorphosed volcanic hosted massive sulfide (VHMS) mineralizations, and albitites. The presence of ecandrewsite in amphibolite, as has been proved for zincian ilmenite and gahnite in other metasedimentary sequences elsewhere in the world, could become another pathfinder or indicator mineral for Zn-enriched portions of the crust.