A lasting legacy of a fetus to the mother is a small number of stably persistent allogeneic cells; the phenomenon known as fetal microchimerism. Prior studies demonstrated that fetal microchimerism in the peripheral blood is associated with protection from breast cancer. Whether the same association of fetal microchimerism extends to the tissue of interest, the breast, is unknown. Total genomic DNA was extracted from frozen normal breast tissue adjacent to invasive disease in women with breast cancer. Control DNA was extracted from reduction mammoplasty tissues from women with no prior history of any breast cancer. The presence of male DNA, presumably from a prior male fetus, was determined with a quantitative PCR assay for the Y chromosome gene, DYS14. Proportions of tissues harboring fetal microchimerism were compared. Thirty-eight cancer-free breast tissues from women with and without a history of breast cancer were evaluable for the presence and quantity of fetal microchimerism testing with the DYS14 assay. Breast tissue from women free of cancer harbored FMc more frequently than normal breast tissue adjacent to invasive disease in women with breast cancer (63 and 26%, respectively). The odds ratio, corrected for total DNA quantity tested, for this protective association of fetal microchimerism against breast cancer was 0.17 (95% confidence interval 0.04-0.76). Findings indicate that the protective association of fetal microchimerism against breast cancer observed previously in the peripheral blood is also reflected in breast tissue.