Cross filter is one of the most useful feature when you are looking for exception report, such as: Open Opportunities without Activities. But, if for some reason you find not able to use Cross Region as screenshot below.
You may see it when using custom report type, no matter the primary object is related to a child object or not. It is caused by the standard ID field not included in the available fields for reports.
With adding ID field as available field in report, for example Opportunity ID for primary object = Opportunity, Account ID for primary object = Account, and so on, will make Cross Filter available again, therefore this is not related to child object.
To add the ID field, navigate to Setup | Create | Report Types, look for the report type name, and click Edit Layout button at Fields Available for Reports and add ID from the primary object for that report type.