Dentin sialophosphoprotein (DSPP) is a phosphorylated parent protein that is cleaved post-translationally into three dentin components: dentin sialoprotein, dentin glycoprotein, and dentin phosphoprotein. In this study we evaluated the dentin sialophosphoprotein expression in human tooth germs to determine its role in tooth development and matrix deposition. DSPP gene expression was investigated performing reverse-transcription polymerase chain-reaction (RT-PCR) and a microarray analysis carried out using high density array containing 21.329 transcripts in replicates. To test for the expression of the DSPP protein, were performed western immunoblot and immunohistochemical analysis during different phases of tissues and matrix formation. All the analysis performed showed high expression level of DSPP in human tooth germs indicating that it may play an essential role for physiological and pathological events in tooth development.