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In Act II, after the Heroes travel through the Sewers and reach the Supermarket, at the very first staircase that they come across that they have to go up. Underneath it, they will find a metal chest and some shopping carts. Next to one will be the Orange Skull.
It is found in the Sewers shortly before the Hero gets to the City Hall. They will be in a small room with a centralized trench full of water. Floaters spawn in the area, so the player must take care. On the right side of the room is a drain. At the back of the drain the player will be on a small platform with a single Walker on the ground sitting against the wall, and a door to the left. Go in the door and on the floor of the room behind some soda and boxes is a pile of pipes with an orange arrow pointing right to the top of them. The player will then be prompted to place the skull on top of the pile.