The growth mechanism in a heteroepitaxy of oxide nanodots is investigated by a combination of x-ray photoelectron spectroscopy (XPS), atomic force microscopy, and theoretical modeling. In contrast to the majority of semiconductor systems, in the studied metal oxide system of Cu2O–SrTiO3(100) the growth process starts without wetting layer formation with the appearance of small (∼10nm) square-based planar Cu2O nanodots. Continued deposition leads mainly to increase of the nanodot density, practically, without change of their size. Only after reaching some critical density (∼1013cm−2 for 760K growth temperature), growth of scattered, significantly larger islands starts through the coalescence of small nanodots. XPS analysis suggests that the interface between small nanodots and substrate is abrupt with only weak Cu–O(SrTiO3) interaction.