Orbs of Transmutation can be used in vendor recipes to make two-stat amulets, using the combinations listed above. They can also be sold for Scrolls of Wisdom, which is a handy way to save space and avoid picking up individual scrolls. Orbs of Transmutation can also be used to purchase goods from vendors, such as various unidentified magic items. Furthermore, one can purchase an Orb of Augmentation in exchange for 4 Orbs of Transmutation from Nessa.

The most common use for Orbs of Transmutation is upgrading a normal item into a magic item, often as the first step in a longer crafting process. The resulting item may have a prefix, suffix, or both, each randomly rolled according to the possibilities afforded the original item, also taking into account its item level.