Most genetic and archeological evidence argue in favor of a recent and unique origin of modern humans in sub-Saharan Africa, but no attempt has ever been made at quantifying the likelihood of this model, relative to alternative hypotheses of human evolution. In this paper, we investigate the possibility of using multilocus genetic data to correctly infer the geographic origin of humans, and to distinguish between a unique origin (UO) and a multiregional evolution (ME) model. We introduce here an approach based on realistic simulations of the genetic diversity expected after an expansion process of modern humans into the Old World from different possible areas and their comparison to observed data. We find that the geographic origin of the expansion can be correctly recovered provided that a large number of independent markers are used, and that precise information on past demography and potential places of origins is available. In that case, it is also possible to unambiguously distinguish between a unique origin and a multiregional model of human evolution. Application to a real human data set of 377 STR markers tested in 22 populations points toward a unique but surprising North African origin of modern humans. We show that this result could be due to ascertainment bias in favor of markers selected to be polymorphic in Europeans. A new estimation modeling this bias explicitly reveals that East Africa is the most likely place of origin for modern humans.