Skulls can appear in place of a rune. If you get one, click on a rune to remove it. These can be used to your advantage: for example, if there is a bunch of runes on the board and there is no space to add one, you can remove one of them so a new one can take its place. These can be discarded just like normal runes, but it's best not to, since doing that will just make the game harder and increase the forge by one level.
As the levels progress and get harder and harder, the chance of getting a skull will be reduced too.