Secreted frizzled-related protein 4 (sFRP4) blocks the Wnt signalling pathway by competitively binding Wnt ligands (frizzled receptors). This pathway is important during development and oncogenesis. It is, however, complex with a large number of interacting proteins, isoforms and receptors. The Wnt signalling pathway has a role in human placental development and implantation, particularly in the trophoblast. Humans and macaque monkeys exhibit a similar remodelling of the decidual spiral arteries. The expression of sFRP4 in human and macaque placentas at different gestational ages have been examined with immunohistochemistry, in-situ hybridization, real-time polymerase chain reaction, and western blotting. This study demonstrates that sFRP4 is expressed predominantly in the villous syncytiotrophoblast and the invasive intermediate cytotrophoblast, and in the amnion. These observational studies suggest that sFRP4 has a role in placental development and implantation, and may be an important factor in the development of the decidual fibrinoid zone, and in trophoblast apoptosis and a band of apoptosis in the underlying decidua deep into the trophoblast.