Mark-recapture experiments showed that D. melanogaster has high dispersal capabilities. Consistent with a highly migratory species, only very low levels of differentiation were described for D. melanogaster populations from the same continent. We reinvestigated the population structure in D. melanogaster using 49 polymorphic markers in 23 natural populations. While European and American D. melanogaster populations showed very low differentiation, Asian D. melanogaster populations were highly structured. Despite the high differentiation of Asian flies, we confirm that all non-African populations are derived from a single colonization event. We propose that the availability of D. melanogaster populations with high and low population structure provides a novel tool for the identification of ecologically important adaptations by hitchhiking mapping.