The parent region for {{isPartOf}} tags should be at the lowest level which still includes everything in the extra region - in the case of a destination which crosses an international boundary, this could be a continent.
Since these regions are extra-hierarchical, they should generally not have any subregions or destinations below them which use them in their breadcrumb trail — the parent region in the real hierarchy should be used instead. When applying this template, it's a good idea to check the destinations listed and change them to the appropriate hierarchical parent.
Once applied, if there is a corresponding hierarchy category, the page will be added to Category:Extra regions with categories for maintenance. Rare exceptions can be made when the child article is itself a valid extraregion, such as the case where the Great Lakes includes Lake Ontario. For such exceptions, add the subregion=yes attribute to the template call, which will prevent the maintenance category from being applied.