This study tests the relative efficacy of human cranial modules, defined on the basis of developmental and functional criteria, for reconstructing neutral genetic population history. Specifically, two hypotheses were tested: 1) The “basicranial hypothesis” predicts that the endochondrally ossifying basicranium will be more reliable for reconstructing population history than intramembranously ossifying regions of the human cranium. This is based on the assumption that early ossification of the basicranium and its distinct functional constraints produce a cranial structure that is relatively immune to non-neutral evolutionary forces. 2) The “single function hypothesis” predicts that cranial regions associated with a single (sensory) function are less reliable indicators of neutral genetic history. Here the prediction is based on the logic that complex, multi-functional, integrated cranial regions are less likely toexhibit homoplasy and, therefore, provide a more accurate morphological proxy for genetic relationships. The congruence between craniometric affinity matrices and neutral genetic population matrices based on autosomal microsatellite and classical markers was assessed using a series of Mantel and Dow-Cheverud tests. The results did not support the predictions of the “basicranial hypothesis,” as the endochondrally ossifying basicranium was not significantly more congruent with the genetic data than intramembraneously ossifying modules. Moreover, although the results provided some support for the “single function hypothesis,” defining cranial modules on the basis of anatomical or functional complexity did not provide a consistent means of predicting their phylogenetic efficacy. These results have important implications for building an accurate inference model of cranial evolution in the human fossil record. Am J Phys Anthropol, 2011. © 2011 Wiley-Liss, Inc.