The massacre in Lisbon was a catastrophic event that marked a violent manifestation of anti-Semitic sentiments in early 16th-century Portugal. After the expulsion of Jews from Spain in 1492 and subsequent forced conversions in Portugal, tensions simmered beneath the surface. By 1506, these tensions erupted violently following an incident in a nearby church, where a supposed miracle triggered unrest among the populace. Rumors spread rapidly, igniting fears and inciting hatred towards the Jewish community, who were largely rich and successful merchants, and deemed scapegoats for various calamities, such as the recent droughts and famine.

Over the course of three days, from April 19 to April 21, 1506, armed mobs descended on the Jewish quarters, armed with clubs and swords. Estimates suggest that approximately 1,900 Jewish individuals were killed, while many more faced terrible violence and their properties were ransacked and destroyed. The local authorities were either unwilling or unable to restore order, allowing the chaos to unfold with little reprieve. Despite the unprovoked violence, the crown later instituted some legal constraints to protect conversos, those who had converted to Christianity but were still seen with suspicion.

The massacre also prompted philosophical and religious debates among the elite, resulting in the exploration of Jewish rights within the wider context of Christianity. Figures such as King Manuel I, who had previously enforced the Jewish conversions, faced pressure to address the repercussions of the violence. The event served to sharpen divisions between Christians and the Jewish community in Portugal, as the legacy of the massacre would haunt subsequent relations for generations.