For investigating the functional genomics of common acute lymphoblastic leukemia (cALL) the gene expression profiles of pathologic leukemic cells and of normal control cells of a corresponding differentiation stage (normal B progenitor cells) are compared. Gene expression profiles from 35 pediatric cALL bone marrow samples, taken prior to anti-leukemic therapy, are analyzed using Affymetrix oligonucleotide DNA-microarrays. The leukemic cells are compared with 15 samples of sorted B lymphocytes taken from cord blood of healthy donors. Differentially expressed genes contain functional information about the cALL molecular pathobiology. Comparison of gene expression profiles demonstrates that the leukemic cells strongly proliferate, which is associated with increased DNA replication and at least not associated with increased protein synthesis. Differentiation of the leukemic cells is arrested in a stage corresponding to late pro B cells. Leukemic cells pursue own anti-apoptotic strategies, e.g. via over expression of apoptosis inhibitors. Certain signaling pathways, especially of the TGFβ/BMP and the WNT family, are active and possibly deregulated in cALL blast cells. These signaling pathways are functioning in a network involved in regulating proliferation and differentiation of B lymphocytes. Deregulation of these networked signaling pathways possibly participates in the cALL lymphoblast’s pathologic phenotype of arrested differentiation and continuous proliferation.