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Although the Umbri tribe once inhabited the surrounding area and controlled land stretching from present-day Tuscany into Le Marche, it was the Etruscans who founded the city, leading to its zenith in the 6th century BC. It fell to the Romans in 310 BC and was given the name Perusia.

During the Middle Ages the city was racked by the internal feuding of the Baglioni and Oddi families. In 1538 the city was incorporated into the Papal States under Pope Paul III, remaining under papal control for almost three centuries.

Perugia has a strong artistic tradition. In the 15th century it was home to fresco painters Bernardino Pinturicchio and his master Pietro Vannucci (known as Perugino), who would later teach the famous painter Raphael. Its cultural tradition continues to this day with the University of Perugia and several other universities, including the famous Università per Stranieri (University for Foreigners), which teach Italian, art and culture to thousands of students from around the world.