Abstract Measures of population differentiation, such as F ST , are traditionally derived from the partition of diversity within and between populations. However, the emergence of population clusters from multilocus analysis is a function of genetic structure (departures from panmixia) rather than of diversity. If the populations are close to panmixia, slight differences between the mean pairwise distance within and between populations (low F ST ) can manifest as strong separation between the populations, thus population clusters are often evident even when the vast majority of diversity is partitioned within populations rather than between them. For any given F ST value, clusters can be tighter (more panmictic) or looser (more stratified), and in this respect higher F ST does not always imply stronger differentiation. In this study we propose a measure for the partition of structure, denoted E ST , which is more consistent with results from clustering schemes. Crucially, our measure is based on a statistic of the data that is a good measure of internal structure, mimicking the information extracted by unsupervised clustering or dimensionality reduction schemes. To assess the utility of our metric, we ranked various human (HGDP) population pairs based on F ST and E ST and found substantial differences in ranking order. In some cases examined, most notably among isolated Amazonian tribes, E ST ranking seems more consistent with demographic, phylogeographic and linguistic measures of classification compared to F ST . Thus, E ST may at times outperform F ST in identifying evolutionary significant differentiation.