Polyploidy is a condition in which cells have more than two sets of chromosomes. Although often associated with erroneous cell division or DNA replication, polyploidy is frequently seen in normal organism development. An excellent example of this is the placenta, where trophoblast giant cells (TGCs) and syncytiotrophoblasts are known to be polyploid. However, the ploidy of other placental cell types, and the regulators of polyploidy in placental development, have not been analysed to date. Now, Jennifer Gerton and colleagues show that the murine placenta is a highly polyploid organ, with multiple trophoblast-derived cell types displaying varying degrees of polyploidy. The authors also demonstrate that Myc is a crucial regulator of this process, since TGCs of Myc knockout mice show decreased levels of polyploidy. By comparing single-cell RNA-seq data of diploid and polyploid cells, they show that polyploid cells display reduced expression of inflammation-associated genes. Additionally, TGCs of Myc-null mice display increased levels of DNA damage and senescence. These observations are attributed to the functions of Myc in DNA replication and ribosomal RNA synthesis. Together, these findings demonstrate that the placenta is more highly polyploid than previously thought, and implicates Myc as an important regulator of ploidy in placental development.