It's happened about four times in the eight months I've had my player. Very rare, but it's certainly memorable when it does happen. Originally it was attributed to the custom equalizer, but I stopped using the EQ after the second time and it's happened twice since. I had one song that would start out fine but turn into a horrendous screech halfway through, always at the same point. I thought the song was bad, but both Rockbox and Winamp on my PC played it with no problems.
For the last month or so I've been using Rockbox almost exclusively so it really hasn't had a chance to happen again...