The yolk sac and aorto-gonad-mesonephros region are well recognized as the principal sites of hematopoiesis in the developing embryo, and the liver is the principal site of hematopoiesis in the fetus. In the present study, we investigated the immunohistoche-mical expression of Glycophorin C (erythrocytes), Neutrophilic elastase (granulocytes), and CD34 (progenitor hematopoietic stem cells, progenitor stromal cells, and vascular endothelial cells) in hepatic parenchyma from fetuses with Down’s syndrome (DS) (16th, 20th, and 24th week of gestational age), and correlated the findings with the equivalent of the hepatic parenchyma from fetuses after spontaneous abortion. Our results did not demonstrate a quantitative difference at the level of erythropoiesis in all three periods examined. In contrast, an important numerical difference was shown in the expression of CD34 positive cells in liver parenchyma from fetuses with DS, in comparison with those found in liver parenchyma from fetuses after spontaneous abortion (p < 0.02). Furthermore, a modest but significant difference was demonstrated at the level of granulopoiesis between the 20th and 24th week (p < 0.01). Given that, the living newborns with Down’s syndrome manifest diverse haematological abnormalities, including a transient leukemoid reaction that usually disappears after some weeks or months, a significantly increased number of CD34 positive and a less significantly increased number of neutrophilic elastase positive cells between the 20th and 24th gestational week could explain this phenomenon in combination with the respective results, if any, in the bone marrow. Regarding our finding of increased stromal CD34 positive cells in the hepatic portal triads, it raises the possibility that a process similar to fibrosis of the bone marrow may contribute to the hepatic fibrosis in DS.