The molecular aspects involved in human implantation include many elements that were first discovered due to their role in cancer cell metastasis. Periostin, a cell adhesion protein that allows the maintenance of cancer stem cells, may influence implantation. The objective of this experimental case-control study was to investigate tissue and serum expression of periostin during pregnancy, and evaluate the potential role of periostin in endometrial receptivity and embryo implantation.Forty-five subjects were included in the final analysis: 15 women who had experienced spontaneous pregnancy loss were enrolled as cases, and 30 healthy pregnant women awaiting voluntary pregnancy termination were enrolled as controls. For both cases and controls, trophoblastic and decidual tissues were collected at 12 weeks of gestation. Periostin expression in decidual and trophoblastic tissues was evaluated by immunohistochemical staining and reverse transcription polymerase chain reaction in cases and controls, and periostin serum levels was analyzed by Western blotting assays in cases, controls and non-pregnant female volunteers.Periostin mRNA and protein levels were higher in decidual and trophoblastic tissues from women undergoing voluntary pregnancy termination compared with women who had experienced spontaneous pregnancy loss. This finding was also reflected at serum level.Periostin may be a serum marker of good endometrial receptivity and embryo quality, and predictive of pregnancy evolution.