This happens to me every now and then, while debugging code and making changes it seems like visual studio caches the pdb information and sometimes it gets stuck. Doing a Rebuild solution, deleting the pdb and creating a new one doesn't fix the problem.
Of course I do have the generate debug information on and all that it's needed, specially since this happens while debugging the code several times.
Visual Studio seems to be happy with the in-memory pdb and refuses to update it, regardless of time-stamps or even size changes in the pdb.
The only way to reset this is to exit Visual Studio (the IDE) and restart it again.
In some rare occurrences, the IDE might be still running in the background (process explorer shows it there) and might hold the handle to the file open. You can kill the process before restarting the IDE.
Good Luck