What do you mean "designated"?
If you mean how do you specify which is the external interface and which is internal, it depends on the router you're using. On a Cisco it's just a single command for each interface (ip nat inside or ip nat outside). On a Netopia the WAN port is always the external interface. On both of these you can then specify the source address to be used, which can be the address assigned to any interface on the router (or an address not even assigned to a port as long as the router has a route for it).
On a Linksys, Netgear, D-Link, any other brand cable/DSL router, the WAN port is always the external NAT interface, and the IP assigned to that port is always the source IP.
Oh yeah, and if you're using Windows ICS, or Wingate/Winproxy, or a Linux/UNIX firewall system, then part of the setup includes specifying which port will be your external and which the internal.