I haven't done it but I see no reason why it would be hard. You just tell it the domain to use which should be able to include the subdomain. One thing is that usually you point the domain's nameserver at the mailinabox server and it sets up all the right records for you. If you can do that on a subdomain then it's super easy. If not you just have to manually set all the records. Mailinabox shows you everything to set if you do it this way though.