Few genetic data document the postglacial history of the western house mouse, Mus musculus domesticus. We address this by studying a sample from the southeastern tip of the Fertile Crescent in the Iranian province of Ahvaz. Including other published and unpublished data from France, Germany, Italy, Bulgaria, Turkey and other places in Iran, altogether 321 mitochondrial D-loop sequences are simultaneously analysed. The patterns of coalescence obtained corroborate the classical proposal according to which the Fertile Crescent is where commensalism with humans has started in the Western Hemisphere, and from where the subspecies has expanded further west. Our data also clearly show that despite multiple colonisations and long-range transportation, there is still a rather high ΦST of 0.39. The original expansion signal is still recognisable, with two well-separated derived clades, allowing us to propose a hypothetical scenario in which expansion toward Europe and Asia Minor took at least two routes, tentatively termed the Mediterranean and the Bosphorus/Black Sea routes. This scenario resembles that of another domesticated species, the goat, and fits with the known progression of Neolithic culture. Given the concomitance of both phenomena around 12 000 years ago, we propose a recalibration of the D-loop mutation rate to a much faster tick of ~40% per site per million years (Myr). This value should be used for intrasubspecific polymorphism, while the interspecific rate in Mus is presently estimated at 6–10%/site/Myr. This is in keeping with the now well recognised fact that only a subfraction of segregating mutations go to fixation.