Tupí linguistic groups display a wide geographical dispersion in South America, probably originated, as pointed by linguistic, from Madeira-Guaporé Region (MGR) in Brazil. The present study reviewed genetic data on Tupians for autosomal and uniparental (Y-chromosome and mtDNA) markers, using it to evaluate Tupians geographic origin as well as the demographic dynamics of their dispersion from a genetic point of view. Comparison of genetic variability and mtDNA haplogroups D frequencies suggests a scenario where MGR is the Tupí homeland. The relationship between five estimators of genetic variability (Thetas-S, -Pi, -m2, -H and -k) shows that Tupí groups from MGR and non-MGR experienced different patterns of demographic dynamics, with an ancient Tupí expansion in MGR, followed by dispersion to other South America regions, probably associated to depopulation/founder effect events. Furthermore, other recent depopulation events could also be detected in both regions. Finally, the dispersion seems to be related to patrilocality, as suggested by comparison of uniparental markers genetic differentiation. This genetic model of dispersion dynamics may have an important impact in the interpretation of archeological and linguistic data, allowing to test if female associated technologies, like ceramic, are more extensively shared between dispersed populations than those which are not female-exclusive.