Heteroepitaxy can involve materials with a misfit of crystal structure. Rotation domains in the epilayer are a fundamental consequence. We derive a general expression for their (minimum) number which is determined by the mismatch of the rotational symmetries of the substrate and epilayer. In the case of a mismatch of rotational symmetry, the number of rotation domains of material A on material B is different from that of B on A. A larger number of rotation domains can occur due to domain structure or nearly fulfilled additional symmetries of the substrate surface.