Gene expression patterns in ductal carcinoma in situ (DCIS) and invasive and metastatic breast tumors have been determined using serial analysis of gene expression (SAGE). The purpose of this approach was to identify biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease. The analyses have led to the identification of several differentially expressed genes, such as HIN-1, dermcidin and S100A7 (psoriasin). The aim of the present study was further to delineate the expression profile of S100 genes using information from 22 breast epithelial SAGE libraries. We demonstrated the down-regulation of S100A6 and S100A10 in breast cancer, irrespective of pathological stage. S100P and S100Z were both up-regulated in cancer; whereas S100A7, S100A8 and S100A9 were strongly up-regulated only in DCIS. The hierarchical clustering of S100 gene expression in these 22 libraries revealed two major groups with distinguishable S100 gene expression profiles. One of them was characterized by the high concomitant expression of S100A7, S100A8 and S100A9. Using SAGE informatics, we found 21 genes with a high positive correlation to S100A7 expression in libraries representing different categories of tissues archived at SAGE Genie, suggesting a function of psoriasin that is not tissue specific. Like S100A7, several of these genes displayed cation-binding properties. We also report the strong correlation in the breast epithelial SAGE libraries between the expression of S100A7 and genes reported as being up-regulated in DCIS, as well as in the inflammatory skin disorder, psoriasis; including RGS5, UPK1A, TMPRSS3, S100A9, p53, SCCA1, SCCA2 and KRT17.