Abstract Biological effects of estrogenic ligands are transduced by two estrogen receptors, ERα and ERβ; they transactivate as dimers. Since ERββ and ERαβ homo- and heterodimers are known to exhibit anti-proliferative effects, we characterized their dimerization interface in atomic details and explored their ligand induced conformational dynamics. ERαβ heterodimer is found to be relatively more stable than the ERββ homodimer and the observed differences are mainly due to loop dynamics. The principal component analysis reveals that, in the essential subspace, the homo- and heterodimer dynamics are distinctively different. The core recognition groove of the dimer interface, formed by helix 9 and helix 10/11, remains unaltered in both homo- and heterodimers. The dimerization surfaces are found to be highly conserved in eukaryotic lineages. Phylogenetic patterns for ERα appear to be very much similar to that of ERβ which signifies that the formation of functional heterodimer is evolutionary selected.