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Intermittent episodes of climate changes, such as those that occurred during the Pleistocene, likely shaped the diversification of the young genus Manihot Mill. (Euphorbiacheae). One of such recently-derived congeners - M. carthagenensis - exhibits a widely disjunct distribution across dry environments in Eastern South America. Herein, we used molecular data from four nuclear gene regions (sts, ch_metE, g3pdh, and nia-i3) and seven nuclear microsatellite loci for reconstructing the phylogenetic relationships among M. carthagenensis and allied species and exploring likely phylogeographic scenarios that shaped the diversification and the distribution of gene pools of M. carthagenensis across the Caatinga and Chaco. Our data suggest that M. carthagenensis is not a monophyletic clade, as presently circumscribed. Morphological differences, genealogical relationships, and vegetation associations support three well-differentiated lineages, each of which merits the species rank: M. carthagenensis, M. glaziovii, and M. hahnii. Microsatellite data suggest that the newly circumscribed M. carthagenensis consists of at least three distinct gene pools, which are partly structured according to geography. The three gene pools likely evolved in allopatry, but remained interfertile. Population expansions after climate amelioration contributed to structuring hybrid zones. Moreover, we described two new single-copy gene regions (sts and ch_metE) as sources of molecular variation; they can facilitate the fine-scale probing of other parts of the phylogeny across Manihot.