Quick answer: Drop runes into the Horadric Cube and hit Transmute. Three of the same rune make the next one up through Thul; from Amn to Pul you add a gem; from Um to Zod you only need two runes plus a gem. The full chart is below — 3 Thul Runes make an Amn (with a Chipped Topaz), 3 Amn Runes make a Sol (with a Chipped Amethyst), and so on.

The full rune upgrade chart

Every rune from El to Zod can be upgraded in the Horadric Cube. The recipe pattern changes three times: plain 3-of-a-kind through Thul, then 3 runes plus a gem from Amn to Pul, then 2 runes plus a gem from Um to Zod. This is the complete, current list for D2R (verified against Patch 3.0):

You getRunesGem
Eld3× El
Tir3× Eld
Nef3× Tir
Eth3× Nef
Ith3× Eth
Tal3× Ith
Ral3× Tal
Ort3× Ral
Thul3× Ort
Amn3× Thul1× Chipped Topaz
Sol3× Amn1× Chipped Amethyst
Shael3× Sol1× Chipped Sapphire
Dol3× Shael1× Chipped Ruby
Hel3× Dol1× Chipped Emerald
Io3× Hel1× Chipped Diamond
Lum3× Io1× Flawed Topaz
Ko3× Lum1× Flawed Amethyst
Fal3× Ko1× Flawed Sapphire
Lem3× Fal1× Flawed Ruby
Pul3× Lem1× Flawed Emerald
Um2× Pul1× Flawed Diamond
Mal2× Um1× Topaz
Ist2× Mal1× Amethyst
Gul2× Ist1× Sapphire
Vex2× Gul1× Ruby
Ohm2× Vex1× Emerald
Lo2× Ohm1× Diamond
Sur2× Lo1× Flawless Topaz
Ber2× Sur1× Flawless Amethyst
Jah2× Ber1× Flawless Sapphire
Cham2× Jah1× Flawless Ruby
Zod2× Cham1× Flawless Emerald

El itself cannot be created — it only drops. There is also no recipe to downgrade a rune, so think before you cube: the trade is one-way.

How cubing runes works

You get the Horadric Cube in Act 2 (Halls of the Dead, Dry Hills) — or from the Act 3 council if you missed it. Put the ingredients inside, press Transmute, and the upgraded rune appears. A few rules that trip people up:

Which runes are actually worth upgrading

Cubing is lossless in rune count but not in trade value. Upgrading is worth it when you are filling a specific gap — the runes for a runeword you are about to make, a crafting recipe, or a Hel for unsocketing. The sweet spot is the mid tier: Ral, Ort, Amn, Thul, Sol, Shael and Hel are cheap to cube up and constantly in demand for runewords like Spirit (Tal Thul Ort Amn) and Insight (Ral Tir Tal Sol), crafting recipes, and socket chores.

Be careful at the top end. Two Bers cube into one Jah, but high runes trade individually at rates that rarely match the 2:1 recipe — you can easily burn value by cubing instead of trading. If you need a Jah or a Ber, check what your spare runes are worth first (our trading sites guide lists where to check prices), then cube only when the math favors it.

One more habit worth building: pick up every Chipped and Flawed gem. They are vendor trash on their own, but they are the fuel for the entire Amn-to-Um ladder — and for gem reroll recipes covered in the Cube database.

Where to get more runes

If you are short on inputs, farm them instead of waiting for luck: the Countess guarantees bonus runes every kill (up to Ist in Hell), and Lower Kurast superchests can drop up to Ber. The full route is in our High Rune Farming guide, and per-rune stats, level requirements and drop sources are in the Runes database. Once you have the runes, Runewords by Level shows what to build at each stage of the game.