The HER2/c-ErbB-2 proto-oncogene is overexpressed in 25-30% of human breast cancers. We previously reported the c-ErbB-2 transcript in mononuclear cells (MNC) from bone marrow (BM), peripheral blood (PB), and mobilized PB (MPB). Here, we describe extensively the expression pattern of c-ErbB-2 mRNA and protein in normal adult hematopoietic tissue and cord blood (CB)-derived cells. Quantitative reverse transcriptase-polymerase chain reaction shows that the c-ErbB-2 transcript is expressed in hematopoietic cells at low levels if compared with normal epithelial and breast cancer cells. The c-ErbB-2 protein was detected predominantly in MNC from PB and CB by Western blot analysis. Flow cytometry revealed that CD15+, CD14+, and glycophorin A+ subpopulations express c-ErbB-2 protein, whereas lymphocytes are c-ErbB-2-negative. The c-ErbB-2 expression is higher in CB MNC. More than 90% of BM- and MPB-derived CD34+ progenitors are c-ErbB-2-negative; by contrast, 5-40% of CB-derived CD34+ progenitors express c-ErbB-2. We found that c-ErbB-2 protein is up-regulated during cell-cycle recruitment of progenitor cells. Similarly, it increases in mature, hematopoietic proliferating cells. This study reports the first evidence that the c-ErbB-2 receptor is correlated to the proliferating state of hematopoietic cells. Studies in progress aim to clarify the role of c-ErbB-2 in regulation of this process in hematopoietic tissues.