I have seen this problem most frequent in wordpress mu 2.8.x
If you have installed a fresh copy of wordpress Mu and you go to the front page and check a post, It shows Page Not found , 404 error.
Well, If you have got his error, It has a very simple fix.
Login as Site admin the
Go to Settings->Permalink and click save.
Go to the front page again and check the posts, It will work 
So, It is not an error, you just need to get your .htaccess updated by resaving, that’s it .
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Fatastic solution! I love it ! It helped me instantly.
Thanks
thanks for the comment. I am glad It helped
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Thanks man you really saved me from hard times. First my images wont show up and then to my surprise I find out that my single post pages are showing the 404 error.
Thanks a lot, you saved me from a terrible night!
I just upgraded and now whenever someone answers s a post (first post is fine) it goes to 404 error. Tried this out but didnt work. Freaking out!
Hi Robert, do you mean when someone posts a comment, he/she is redirected to 404 page ? what do you see in the url where 404 page is generated. That may help to resolve it.