The chemical reactivity of thin layers (ca. 10 nm thick) of ZnO deposited onto differently oriented Al 2 O 3 single crystals has been investigated by means of atomic force microscopy inspections and X-ray absorption spectroscopy at the Zn–K edge. The (0001) ZnO∥(11 2¯ 0) sapphire interface yields the ZnAl 2 O 4 spinel and a quite stable film morphology. Instead, the (11 2¯ 0) ZnO∥(1 1¯ 02) sapphire and (0001) ZnO∥(0001) sapphire interfaces give origin to a new compound (or, possibly, even two new compounds), whose chemical nature is most likely that of a ZnO/Al 2 O 3 phase, with still unknown composition and crystal structure. In addition, in the last two cases, films collapse into prismatic twins of ca. 1 μm in dimension. These experimental findings demonstrate that in a solid-state reaction, the topotactical relationships between the reacting solids are of crucial importance not only in determining the kinetic …