The Mongols under Janibeg besieged Kaffa and the Italian enclave at Tana, following a brawl between Italians and Muslims in Tana. The Italian merchants in Tana fled to Kaffa. The siege of Kaffa lasted until February 1344, when it was lifted after an Italian relief force killed 15,000 Mongol troops and destroyed their siege machines. Janibeg renewed the siege in 1345 but was again forced to lift it after a year, this time by an epidemic of plague that devastated his forces. The Italians blockaded Mongol ports, forcing Janibeg to negotiate, and in 1347 the Italians were allowed to reestablish their colony in Tana.

The spread of the plague through the ranks of the Mongols demoralized the army, and a large bulk of them lost interest in the siege. However, the Mongols would not back off, not without giving Kaffa a piece of their own torment. They put the corpses of their dead on their catapults and flung them over the defensive walls of Kaffa. The dwellers of Kaffa watched as rotten bodies fell from the skies, crashing on their soil, spreading their putrid smell in all directions. The Christians could neither hide nor flee from the havoc that rained down upon them. They moved as many rotten bodies as they could, dumping them into the sea as quickly as they could. But by then, it was too late; the Black Death was already in Kaffa. Fleeing inhabitants may have carried the disease back to Italy, causing its spread across Europe.;