Highly controlled biomineralization of calcium carbonate is via non-classical mesocrystallization of amorphous precursors. In the present study, a simple in vitro assay was developed to mimic the biological process, which involved stabilized amorphous calcium carbonate and a single crystal substrate of calcite. The microcoating layer formed on the calcite substrate displayed mesocrystalline characteristics, and the layers near the substrate were strongly influenced by the epitaxy to the substrate. This behavior was preserved even when the morphology of the coating layer was modified with poly(acrylic acid), a model anionic macromolecule. Interestingly, the extent of the epitaxy increased substantially with poly(ethylene imine), which barely affected the crystal morphology. The in vitro assay in the present study will be useful in the investigations of the biomineralization and bioinspired crystallization of calcium carbonate in general.