Spiders have not traditionally followed the src= attribute. All other links (the ones that change the iframe's content) look "vanilla" to a spider, as indeed they are - they only add in a target attribute to address the iframe.
I've found it helpful to ensure that somewhere or other in the website there is a straight HTML link to the original document in an iframe, the one loaded by the src attribute. That link can even be in the site map, but that's my only caveat.
And of course, it very useful to have some kind of scripting to help the visitor who arrives at your iframe intended page, but orphaned from its parent. At the very least, make sure there is on-page navigation in any iframed document to allow visitors to access your full site.