Skeleton Keys are items that allows the player to unlock additional upgrade choices at the Mirror of Night and additional Infernal Arms. During a run they can be spent to unlock Trove Trials.
||'...Certain artifacts within the realm of Hades have been sealed under lock and key, to prevent tampering by those not yet prepared to harness their immeasurable might. Those keys are not so easy to procure. But, there are ways. The keys lie strewn within Tartarus, perhaps beyond. True to their namesake, they crumble to dust when used; but the dust merely reforms, in time.'
Skeleton Keys can be found as room clear rewards (1 for normal rooms; 2 for "challenge" rooms).