Selective inhibitors of protein kinase CK2 with significant cytotoxicity on tumor cells based on a 2-aminothiazole scaffold were described recently. Here, these studies are supplemented with representative CK2α/CK2α' complex structures. They reveal that the 2-aminothiazole-based inhibitors occupy the ATP cavity, whereas preliminary data had indicated an allosteric binding site. The crystal structure findings are corroborated by subsequent enzyme kinetic studies; their atomic-resolution quality provides the basis for future optimization of these promising CK2 inhibitors.