Our studies are aimed at determining whether pregnancy induces a specific genomic signature in the postmenopausal breast that is responsible for the protective effect elicited by this physiological process. For this purpose we designed a study to compare the gene expression profiles in normal breast tissue from parous postmenopausal women with (case) and without (control) breast cancer. We have used breast samples from 18 parous controls and 41 parous cases. The epithelium and the interlobular stroma were dissected using laser capture microdissection and the RNA of each compartment and each sample was isolated, amplified using PCR methodology, and hybridized to cDNA glass-microarrays containing 40,000 genes, placing the human reference RNA in the green channel (Cy3) and the breast tissue samples in the red channel (Cy5). The normalization and statistical analysis of the expression data were carried out by using the LIMMA software package for the R programming environment which provides functions to summarize the results using the linear model perform hypothesis tests and adjust the p-values for multiple testing. We were able to identify 126 genes that were upregulated and 103 that were downregulated in the parous control group. There were only 56 genes differentially expressed in the interlobular stroma in the parous control group in relation to the other group of women under study. The gene categories that were overrepresented in the breast epithelium of the parous control breast are related to apoptosis, DNA repair, response to exogenous agents and transcription regulation. In the present study we demonstrate that full-term pregnancy imprints a specific genomic signature in the breast epithelium of postmenopausal parous control women that is significantly different from women who have developed cancer. This genomic signature induced by pregnancy could help to predict in which women parity is protective.