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I was performing a test migration from Exchange 2010 to Office 365 using a domain I used to host on my cPanel server. The domain had been removed from cPanel but I was receiving a 550-Unroutable Address error when testing email each way.

The NDR looked similar to:

Diagnostic information for administrators:

Generating server: bigfish.com

me@somewhere.com
my.server.com # 550-Unrouteable address 550 Sender verify failed> #SMTP#

In my case, when I removed the domain from cPanel, it was not removed from /etc/localdomains. I manually removed it from that file and then mail was delivered as normal.