Previous studies have shown that human and mouse placentas have hematopoietic potential during mid-gestation. In this investigation, we used histological and immunohistological approaches to visualize hematopoietic cells in mouse placenta between 9.5 and 12.5 days of gestation (gd), identifying their topography and niche. Putative hematopoietic foci were present on 10.5 and 11.5 gd but not 9.5 or 12.5 gd and was restricted to the placental labyrinth. Two major niches each with distinctive hematopoietic cell clusters were present. One type of hematopoietic cell cluster involved the chorioallantoic vasculature and fetal vessels near the chorionic plate. These clusters resembled the hematopoietic stem cells produced by large embryonic arteries such as aorta that persist in postnatal marrow. The other type of hematopoietic cell cluster identified was at the opposite side of labyrinth next to the junctional zone and was composed of erythropoietic foci. Our results suggest that mouse placenta not only produces hematopoietic stem/progenitor cells but also a second wave of primitive erythrocytes that may support a rapid, mid-pregnancy, fetal growth trajectory. Our data also point to a close relationships in the origins of hematopoietic and endothelial cells within placenta.2030-01-01