How rune upgrades work (Horadric Cube)
Place the ingredients in the Horadric Cube and transmute. From Eld up to Thul, three copies of the same rune cube into the next one with no gem required. From Amn onward a gem is added, and from Um onward you only need two copies of the previous rune. In D2R every recipe works in all modes — the old ladder-only restrictions from classic Diablo II were removed, so single-player and non-ladder characters can cube all the way to Zod.
The recipe to create each rune is listed on its card above. As a rule of thumb, cubing your way to high runes is almost never worth it — the gem and copy counts grow exponentially — so treat the cube as a way to clean up mid runes, not as a path to Ber.
Where to farm runes
The Countess (Forgotten Tower, Black Marsh, Act 1) has a special rune drop on top of her normal loot: it caps at Ral on Normal, Ko on Nightmare and Ist on Hell, which makes her the standard source for low and mid runes. For high runes (Lo, Sur, Ber, Jah), density is everything — farm areas packed with monsters such as Chaos Sanctuary, Travincal, the Secret Cow Level and high-level Terror Zones. See the farming guide below for routes.