Various signaling molecular pathways are involved in odontogenesis to promote cellular replication and differentiation. Tooth formation is controlled mainly by epithelial–mesenchymal interactions. The aim of this work was to investigate how cellular replication and differentiation ensue during the formation of the murine first molar in postnatal ages until eruption, focusing on morphogenesis, odontoblast differentiation and cellular replication. Wild-type CD1 mice were examined from birth to weaning. Morphogenesis and interaction between developing epithelial and mesenchymal tissues were evaluated in hematoxylin–eosin and Gomori trichome stained sections. Immunohistochemistry for nestin, which mediates the differentiation of odontoblasts, especially their polarization and elongation, showed that this intermediate filament was apparent already at postnatal day P1 in the apical region of odontoblasts and progressed apically from cusp tips, while it was not present in epithelial tissues. The expression of nuclear antigen Ki-67 highlighted dividing cells in both epithelial and mesenchymal tissues at P1, while one week later they were restricted to the cementoenamel junction, guiding root elongation. The link between odontoblast maturation and cellular replication in the different tooth tissues is essential to understand the development of tooth shape and dimension, to outline mechanisms of tooth morphogenesis and possibly eruption.