Instructions
Right-click the Horadric Cube to open it. Unless you placed the Cube in your bank, it will appear in your inventory, which you can access by pressing "I" on your keyboard.
Place items that will result in a successful transmutation into the Cube by clicking the item and clicking the empty space inside the Horadric Cube. For example, three gems of the same type will transmute into a gem of higher quality. If you're unsure of the available Horadric Cube recipes, visit Blizzard's Battle.net Horadric Cube site for a list of all in-game recipes.
Click "Transmute" in the Horadric Cube window. If the contents inside the Cube are transmutable, a new item will appear.