The first doctrine to be outrightly rejected in the history of the world

The serpent first questioned God's word by asking Eve if God had really said that they could not eat from the tree.

The serpent then goes on to outrightly reject God's word, which was a word on the doctrine of judgement:

But the serpent said, 'you will not surely die' - Genesis 3:4

(Thanks to Josh Etter for the concise reminder. This doctrine is the one I'm tempted to push just slightly to one side, most of the time, yet when I'm reminded of it, is the one that makes me flee to Christ time and again)