Runes that are single can be dropped anywhere throughout Diablo 2: Resurrected, beginning with Normal difficulty until into Hell difficulty D2R Ladder Items. Runes can be socketed, the same as gems. That means they can be placed in equipment with sockets to benefit from their effects. However, the true magic of running stones is when you combine them in a specific order in specific items.
They're called runewords, are some of the most useful items you can find to be found in the game and are right ahead of sets and exclusives. A full list of all runewords is available in the next section.
Runes may also be used in specific Horadric Cube recipes. For example, you can combine a Ral rune together with a damaged piece equipment to fix it. This is a good idea to use when you're short of gold and are unable to afford repairs at a vendor.
Runes may also be combined with one another in the Horadric Cube; this is commonly referred to as "cubing to" and is a common way to climb to the next rune without having to find that rune in the wild. For instance, if you already have 3 El runes and need an Eld rune Buy D2R Ladder Items, place three El runes in the cube by pressing the transmute button. Out will come an Eld rune. This recipe for upgrading is available in the rune chart to the left.