© 2014 MP Publishing LLC. We show that yttria-stabilized zirconia (YSZ) films deposited on structurally dissimilar SrTiO3(l 10) substrates exhibit two-dimensional layer-by-layer growth. We observed that, up to a thickness of about 15 nm, the square (001) basal plane of the cubic YSZ grows epitaxially on the rectangular (110) crystallographic plane of SrTiO3 substrates, with 1110]YSZ(001)//SrTiO3(l 10) epitaxial relationship. Thus, the heterointerface presents symmetry discontinuity between the YSZ(001) film and the lower surface symmetry SrTiO3(110) substrate. Beyond this specific case, we envisage similar approaches to develop other innovative oxide interfaces showing similar crystal symmetry discontinuities.