I think I had this same problem.
On the site I was looking at the lightboxed images perform normally on all pages except one, where they appear on their own in the window rather than in a lightbox. Originally they appeared normally, then without any change of theme, wordpress version, or plugin, the lightbox stopped working after a page edit.
When the link is clicked, the page starts to be be darkened as if a lightbox was starting, but then instead of the image appearing in the middle of the page, it flicks over as if an ordinary link had been triggered.
The site I looked at had:
Custom theme (but WordPress Default 1.6 did exactly the same)
Freesouldesign, no, it's not a page load issue in this case. You can load the page and leave it for 5 mins before you try the links, and they still won't work. Different browsers and different machines all show exactly the same behaviour.
I went through the code of the page carefully, and discovered that there was a place where an image had been deleted. The img tag had been removed, but the a href tags around the image were still lurking invisibly in the HTML. I assume that the WYSIWYG editor that the site owner was using did this accidentally when he tried to remove a photo by selecting it and pressing 'delete': it didn't delete all the code.
<a href=""...></a> from the code fixed the problem on the site I was looking at. So if you have this issue, may be worth zapping the images in your post, then go into HTML view on your editor and remove any links that they may have left behind, then re-add the pics.