The TiSi2/Si system is investigated using high‐resolution transmission electron microscopy (HRTEM) and electron diffraction in both cross‐section and flat‐on modes. The results show that the large crystallographic differences between both crystals and the complexity of the reaction path are not obstacles to the formation of flat and well‐defined interfaces. (1¯01) TiSi2proves to be a preferential plane for epitaxial growth on Si (111). In this case, the terminal TiSi2plane at the interface is composed of single atomic species. It is proposed that the reasons leading to such an epitaxy are related to the small discrepancy of atomic densities and interplanar spacings characteristic of these planes. Observation of local epitaxial relationships are reported and investigated using a lattice matching model. It turns out that they minimize the two‐dimensional misfit at the interface.