Transferrin receptor/CD71 is a membrane protein expressed on nucleated red blood cells (NRBCs) and trophoblasts. Here, we propose the first study to evaluate the usefulness of CD71 immunolabeling in the main fields of gestational pathology. To this aim, formalin-fixed, paraffin-embedded samples of 45 orthotopic (23 spontaneous abortive and 22 molar pregnancies) and 11 ectopic pregnancies were immunostained for CD71. NRBCs were morphologically evident in 23 cases: 12/23 abortive, 4/11 ectopic, and 7/10 partial molar pregnancies. CD71 immunolabeling detected NRBCs in all 23 previous cases and in 8 new cases: 2 partial moles and 6 spontaneous abortive pregnancies. No NRBCs were detected in complete moles by means of either morphology or immunohistochemistry (IHC). In 4 cases with extensive necrotic changes, CD71 marked NRBCs and a few ghost villi, which were not certainly identifiable with standard histological evaluation. Furthermore, there was an inversely proportional relationship between total percentage of CD71-positive NRBCs and gestational age (R=0.69; P<0.0001). We conclude that CD71 is a robust IHC marker for the detection of NRBCs and chorionic villi, especially in the presence of necrosis. The demonstration of NRBCs can be important in molar pathology, helping to exclude a complete mole. The application of CD71 could improve the diagnosis of this pathology in selected cases in which diffuse necrotic or hemorrhagic aspects may hinder the interpretation of the conventional approach with histology, IHC for p57, and ploidy analysis. Finally, the inverse correlation between the total percentage of CD71-positive NRBCs and gestational age suggests that this analysis may help in pregnancy dating.