Runes that are single can be dropped anywhere within Diablo 2: Resurrected, beginning in Normal difficulty and moving up on to Hell difficulty D2R Ladder Items. Runes are a socketable item, just like gems, meaning they can be placed in the socket of your gear to  gain their effects. However, the real value of runes comes when you put them together in a specific sequence in an item. The runewords, which they're also called are among the most useful items within the game and are right between established items and specials. A complete list of the runewords can be found in the next section.

They can also be employed in specific Horadric Cube recipes. For example, you can mix a Ral rune and a damaged piece gear to repair it. This is a great trick when you're low on gold and can't pay for repairs through a vendor. Runes can also be grouped into the Horadric Cube; this is colloquially called "cubing in" and it is a typical method to move to the next rune without needing to locate its location in wild. For example, if you already have 3 El runes but need one more, place three El runes inside the Cube and hit the transmute key. The result will be the Eld rune. This recipe for upgrading is found in the rune table below.

The quest of Hellforge found in Act 4 will always drop the runes. In fact, it often serves as a form of payment to speed up the various acts. The Countess's abode, which can be found at the base of the Forgotten Tower in Act 1's Black Marsh, is another great source of runes.

Because the runes are a set limit of rarity, which ranges from most frequent (El) through to the rarest (Zod) typically, they're utilized as an economic tool in Diablo 2. El up to Lem are usually considered to be low runes. Pul to Gul are typically regarded as mid runes, while Vex and Zod are usually considered high runes D2R Ladder Items Buy. If you spot middle or high runes while on your travels, be sure to not part with them easily!