If your theme's index.php page has a call for a max number of posts, it has to match your WordPress settings under Reading for "Blog pages show at most". For example, if your theme's index.php page has a query call such as query_posts("cat=-27,-28&paged=$page&posts_per_page=5"), the max posts here is 5. But if your "Blog pages show at most" setting is 10 (the default), there is a mismatch. This will trigger the 404 error page.
The solution is to have both match. In this example, you can simply change "Blog pages show at most" to 5, or posts_per_page=5 to posts_per_page=10.