Syndecans belong to a 4‐member family of cell surfaceheparan sulfate proteoglycans (HSPGs) abundantly presentin various tissues. They are primarily recognized as extra-cellular matrix (ECM) receptors with ability to bind variousECM components and form gradients of growth factorsand morphogens. Syndecans are composed of core protein(PG backbone) with distinctive cytoplasmic, transmem-brane and extracellular domain to which several HS gly-cosaminoglycan (GAG) chains are covalently attached. Indevelopment of composite organs such as teeth, the expres-sion patterns of syndecans were previously reported todisplay temporo‐spatial shifts between epithelial andmesenchymal tissue compartments. Along with diversefunctional properties of syndecans and generally large num-ber of their interactors due to HS GAG chain content, thissuggests possible involvement of syndecans in modulationof epithelial‐to‐mesenchymal crosstalk. Functional versatil-ity of syndecans significantly depends upon the biochemi-cal properties of attached HS GAG chains. These aredetermined during the HS biosynthesis by the combinato-rial action of glycosyl‐transferases (Exts/EXTs) and bi‐functional sulfotransferases (Ndsts/NDSTs), as well as bypost‐biosynthetic enzymatic cleavage of HS by the onlyactive endo‐glucuronidase in mammals, heparanase 1(Hpse1/HPSE1). Corresponding to the essential requirementfor HS during organogenesis, null‐mutant animals for genesencoding these enzymes display severe developmentalanomalies of mineralized tissues (including teeth) withembryonic or perinatal lethality. Here, we analyzed expres-sion of syndecan HSPGs (Sdc 1, 2 and 4), enzymesinvolved in HS biosynthesis (EXT1, NDST1, NDST2) andHS cleavage (HPSE1) in human tooth germs during theearly stages of odontogenesis. We used samples of fetal tis-sues from ten human conceptuses aged 7/8 (n= 3), 11/12(n= 3) and 14 weeks of gestation (n= 4) stored as histo-logical sections as a part of fetal human archival collectionof the Department of Anatomy, Histology and Embryology(University of Split School of Medicine). Immunofluores-cence staining was performed. Several methods for quan-tification of fluorescence were applied including intensitycorrelation analysis (for co‐localization of signals), densito-metry (3D surface plots and vertical plot profiles), and sta-tistical analysis of total surface covered by expressiondomains using Kruskal‐Wallis and Dunn's multiple compar-ison test (statistical significance was set atP< 0.05). Allof the investigated factors showed temporo‐spatial differ-ences of expression patterns, while some of them displayedvery distinctive asymmetries of expression domains. Ourfindings suggest that these factors might be differentiallyinvolved in cellular processes which take place during theearly odontogenic sequence in humans. The analysis ofexpression patterns of investigated enzymes involved in HSbiosynthesis and HS degradation also indicates that multi-ple and mutually distinctive roles attributed to syndecans inregulation of cellular processes during odontogenesis mightbe derived from variations from variations in compositionand biochemical properties of attached HS side chains.