Matt Quackenbush submitted this unusual behavior a few days ago and I was finally able to reproduce and fix today. Here is his excerpt:

If I browse to http://localhost/myApp/index.cfm/main/dspHome (or any other explicitly-called event), everything is good to go. However, if I browse to http://localhost/myApp/ or http://localhost/myApp/index.cfm, an exception is thrown that says: The event handler: index.cfm.dspHome is not valid registered event.

The problem was the cleaning of the path info and cgi script name in the ses interceptor. The fix is on SVN and also attached to this post. It is a single file ses.cfc Just grab it and overwrite the original ses.cfc interceptor in your coldbox installation, which can be found at:

/coldbox/system/interceptors/ses.cfc

That's it folks. This bug has also been registered and will be available on the daily builds, SVN and the next major milestone. I will also be updating the 2.5.1 build with the updated file.