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The second quest in Act IV can be activated first if you talk to Deckard Cain before Tyrael:

Deckard Cain
The time has come to destroy Mephisto's Soulstone!
Although I picked it up before entering the Infernal Gate, I believe you should carry out this crucial mission.
Take the Stone to the Hellforge. Place it upon the forge and strike it soundly with the Hammer.

Only by doing this can you prevent Mephisto from manifesting in this world ever again.
DII Icon Hell's Forge.png Hell's Forge
Take Mephisto's Soulstone to the Hellforge.

If you didn't pick up Mephisto's Soulstone when you killed him then Deckard Cain did so, and he gives it to you when you talk to him: it requires one inventory space.

Surprisingly, this 'crucial mission' is optional: as far as the plot is concerned, if you don't complete it then you must destroy Mephisto's and Diablo's Soulstones together (although killing Diablo first doesn't prevent you from completing this quest in a later game).

The Hellforge can be found in the River of Flame, beyond the Outer Steppes, Plains of Despair and City of the Damned.

City of the Damned

The City of the Damned is randomly populated by three of the following seven monster types: Abyss Knights, Corpse Spitters, lightning-spitting Damned, roosting Dark Familiars, fire-breathing Pit Lords, mana-draining Stranglers and Stygian Hags (which spawn Stygian Dogs). There are also Trapped Souls, and there can also be corpse-spitting Maw Fiends, and Windows.

The stairs down to the River of Flame are somewhere in the City of the Damned, and there's a waypoint nearby.

River of Flame

The River of Flame is randomly populated by three of the following seven monster types: Abyss Knights, Blood Maggots (which spawn Blood Maggot Eggs, which in turn spawn Blood Maggot Young), Grotesques (which spawn Grotesque Wyrms), corpse-spitting Maw Fiends, fire-breathing Pit Lords, mana-draining Stranglers, and Urdars.

The waypoint is always to the northeast, where the angel Hadriel guards the final approach to the entrance to the Chaos Sanctuary. If you talk to him before completing this quest:

Hadriel
Halt! Before venturing into Diablo's lair, go to the Hellforge with Mephisto's Soulstone.

Place the stone on the Hellforge and use the Hellforge Hammer to destroy it.

However, he doesn't actually stop you from traveling beyond him to the Chaos Sanctuary.

The Hellforge is always at the end of a spur of rock to the northwest or southeast. Approaching it will trigger this quest if talking to Deckard Cain hasn't already done so:

DII Icon Hell's Forge.png Hell's Forge
Destroy Mephisto's Soulstone at the Hellforge.

At this point, you should start clearing the approach to the Hellforge before you encounter its guardian...

Hephasto the Armorer

Super Unique Demon (Spectral Hit Aura Enchanted)

Your soul shall fuel my Hellforge!

Hephasto needs to be killed, as he drops the Hell Forge Hammer required to destroy Mephisto's Soulstone upon the Hellforge. He has Poison Resist -50% in Normal and Nightmare, and none in Hell. Although not as fearsome as in earlier versions of the game, his aura may augment not only his own power, but that of any other monsters in its area of effect, and Knockback can still be useful to pin him against an obstruction or the shore of the river.

Hell Forge Hammer

Hell Forge Hammer
  • One-Hand Damage: 6 to 15
  • Durability: 55
  • Mace Class - Speed 0
  • Adds 5-20 Fire Damage
  • +35 Defense
  • Fire Resist +40%
  • +50% Damage to Undead

It requires 3x2 inventory space. After placing Mephisto's Soulstone on the Hellforge:

DII Icon Hell's Forge.png Hell's Forge
Use the Hellforge Hammer on the Forge.

Equip the Hell Forge Hammer and strike the Forge three times to destroy Mephisto's Soulstone, releasing the souls trapped within. A selection of random gems drops from the Hellforge: one perfect, two flawless and one normal quality.

Diablo II: Lord of Destruction
Diablo II: Lord of Destruction

One of the following runes also drops:

Difficulty Rune
Normal El Eld Tir Nef Eth Ith Tal Ral Ort Thul Amn
Nightmare Sol Shael Dol Hel Io Lum Ko Fal Lem Pul Um
Hell Hel Io Lum Ko Fal Lem Pul Um Mal Ist Gul
DII Icon Hell's Forge.png Hell's Forge
Quest completed.
DII Icon Hell's Forge.png Hell's Forge
You completed this quest in a previous game.

If you talk to Deckard Cain:

Deckard Cain
Congratulations, hero!

Surely, even Diablo, himself, sensed the fury unleashed when you smashed his Brother's Soulstone.