Objective: To investigate the spatial and temporal expression of proliferation Ki-67 marker, pro-apoptotic (Bax, caspase-3 and p53) and anti-apoptotic (Bcl-2) proteins and differentiation markers (Hsp70 and syndecan-1) during early development of the human tooth. Materials and methods: Paraffin serialsections of developing teeth in 13 normal human conceptuses, 5–12 postovulatory weeks old, were stained using immunohistochemical (DAB) and immunofluorescent techniques. Distribution and intensity in expression of different markers was analyzed using semi-quantification, while percentage of Ki-67 positive cells was analyzed by statistical tests. Results: Proliferation activity (Ki-67) is present in both epithelial and ectomesenchymal parts of tooth germs: it first increases till the 8th developmental week, then gradually decreases in the tooth bud and increases in the ectomesenchyme. Bcl-2 is strongly expressed in proliferating cells, moderately in the tooth bud, and weakly in the ectomesenchyme. Co-expression of Bcl-2 and Bax was found in majority of the tooth germ cells: Bax prevailed in the outer enamel epithelium and ectomesenchyme, while Bcl-2 prevailed in the inner enamel epithelium and the enamel pulp. In earlier developmental stages, caspase-3 positive cells were found in the jaw ectomesenchyme, and from the 9th week on in the epithelial tooth bud, as well. P53 positive cells were first found in the jaw and tooth ectomesenchyme, and from the 9th week on, also in the epithelial tooth bud. During all investigated stages, Hsp70 displayed stronger expression in the epithelial part, and syndecan-1 in the ectomesenchymal part of the tooth germ. Conclusions: Proliferating cells most likely influence growth of the whole tooth germ, while Bcl-2 affects proliferation and differentiation of specific cell lineages. Bax influences process of cell death in parts of the tooth germ that should disintegrate during development, caspase-3 most likely affects enamel knot and enamel pulp disappearance, while p53 controls proliferation. Hsp70 and syndecan-1 probably participate in tooth germ cell proliferation and differentiation.