A sliver broke off from the Black Soulstone when Malthael took it, and Tyrael attempts to use it to discover Malthael's plans. Tyrael reveals that with Diablo gone, Malthael sees humanity as a race of demons based on their descent from the original Nephalem, the offspring of angels and demons by wiping out humanity, Malthael hopes to end the Eternal Conflict, the long war between Heaven and Hell. With the gates blocked, the Nephalem fights through the city sewers to the Zakarum cathedral in the city center, where they encounter Tyrael. Nahr encounters the Nephalem outside Westmarch City, which has been overrun by the Reapers, Malthael's army of enslaved spirits and renegade angels.

Tyrael sends the surviving Horadrim, Lorath Nahr, to locate the Nephalem. Now calling himself the 'Angel of Death', Malthael kills all but one of the Horadrim, incapacitates Tyrael in the process and steals the Black Soulstone. However, the group is ambushed by Malthael, former Archangel of Wisdom and member and leader of the Angiris Council, who had disappeared after the destruction of the Worldstone after it was corrupted by Baal twenty years earlier (at the end of Diablo II: Lord of Destruction). Knowing it is too dangerous to leave in the hands of mortals or angels, he and six Horadrim take the Black Soulstone back to Sanctuary and attempt to seal it away where it can never be found - deep in the tomb of Rakkis, the first King of Westmarch, the kingdom established to the west of Khanduras. After Diablo is defeated by the Nephalem (the player character), Tyrael recovers the Black Soulstone that contains the essence of all seven of the Great Evils.

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