One of the weirdest support tickets I've ever worked:

Customers FedEx Ship Manager Software couldn't read/write to servers. It was connecting. They were reachable, and pingable. Traffic was flowing through the firewall, but the software and servers were getting malformed packets.

Turned out, the customers firewall had deep packet inspection turned on, and their DPI routine had bug in it. It would mangle packets when rebuilding them for transmission.