Using oligonucleotide microarrays we recently identified a set of transcripts that were up-regulated in hypoxic human trophoblasts. To test the hypothesis that expression of hypoxia-related placental transcripts depends on sampling site we analyzed nine different sites from term human placentas (n = 6), obtained after uncomplicated pregnancies. These sites spanned the placental center to the lateral border and the basal to the chorionic plate. Relative gene expression at each site, determined using quantitative PCR, was correlated with villous histology. The expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF), the cytoskeleton proteins lamininA3 and α-tubulin, and the signal transduction protein Rad was enhanced in the subchorionic lateral border compared to medial basal site (1.6-2.9 fold, p < 0.05). In contrast, the expression of NDRG1, adipophilin and human placental lactogen was unchanged. Enhanced villous maturation, syncytial knots and fibrin deposits were more frequent in the subchorionic placental lateral border, and correlated with up-regulation of hypoxia-related transcripts (p < 0.05). The association between sample site and expression level was not observed in placentas with marginal cord insertion. The expression of hypoxia-related genes in the term human placenta is dependent on sampling site within the placental disk, likely reflecting local differences in villous perfusion.