Paul III established the Congregation of the Holy Office in 1542, in the bull Licet ab initio, at a moment when Protestant teaching was spreading into Italy and the papacy judged the existing, largely local, machinery of the medieval inquisition inadequate to the threat. The new body was centralized in Rome under a small group of cardinal inquisitors and could direct proceedings across Catholic Europe, though in practice its authority was strongest within Italy itself and weaker in kingdoms, such as Spain, that maintained their own separate tribunals answering to the crown rather than to Rome.
The Roman Inquisition's caseload extended beyond suspected Protestants to include magical practice, moral offenses, and, from the early seventeenth century, philosophical and scientific claims that appeared to conflict with scripture as the church then read it. Giordano Bruno, tried over several years on charges that combined heretical theology with cosmological claims, was burned at the stake in Rome in 1600 after refusing to recant. Suspects who cooperated and recanted generally received penances rather than execution, and the Congregation kept written records of its proceedings far more systematically than most secular courts of the period, part of why its case files remain an unusually detailed source for historians of early modern belief and dissent.