Objective Erythropoietin (Epo) is known to regulate the number of circulating erythrocytes. Epo receptor (Epo-R) expression is limited to few organs including the uterus. We investigated differences in Epo and Epo-R expression in normal and disturbed first trimester human pregnancy. Study design Placental tissue was obtained from normal human pregnancy, abortion and hydatidiform mole during the first trimester of pregnancy. Epo and Epo-R expression was investigated by Immunohistochemistry and real time PCR (TaqMan ®). The intensity and distribution patterns of Epo and Epo-R expression were evaluated by using a semi-quantitative method (immunoreactive score) as previously described. Results Epo-R expression was upregulated in the villous trophoblast (VT) of abortive tissue ( p = 0.002) as compared to normal pregnancy. This was further confirmed on mRNA level. With regard to mole pregnancy, Epo-R expression was also significantly increased in the VT ( p < 0.001). In extravillous trophoblasts (EVT), only Epo, not Epo-R expression was significantly increased in abortive tissue ( p = 0.006) as well as in hydatidiform mole ( p = 0.041) in comparison to normal pregnancy. Identification of EVT as Epo-and Epo-R-positive cells was obtained by double immunofluorescence with CK7 and Epo/ Epo-R double staining. Both mole pregnancy and abortion were accompanied by an upregulation of Epo ( p = 0.041; p = 0.018) and Epo-R expression ( p = 0.007; p = 0.015) in decidual tissue as compared to normal pregnancy. Conclusion Within our study we were able to demonstrate increased expression of Epo and Epo-R in abortive tissue and hydatidiform mole. Whether upregulation of Epo and Epo-R is secondary to placental hypoxia as part of the abortion process or a risk factor of its own, needs to be further investigated.