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Domenico was born in Valdibiena, near Siena, in 1486. He studied the works of Pietro Perugino, who stayed in the city between 1502 and 1509. He also studied the works of Sodoma and Raphael and he paid close attention to their way of using colors and light effects. His painting is characterized by strong contrasts of light, shadows and colors, which make the scenes seem unreal, almost like visions.
Beccafumi was well-informed on the latest Florentine works of his time, especially the paintings of Fra Bartolomeo, Piero di Cosimo, Mariotto Albertinelli and the first mannerist painters. In fact, he might have spent his early years in Florence.
He certainly was in Rome around 1510, where he studied the works of Michelangelo and Raphael. In 1512 he returned to Siena, where he was influenced by the works of Sodoma and especially by his studies of anatomy and nude figures. In this period he received his first important commissions like the decoration of the façade of Palazzo Borghesi and the chapel of Madonna del Manto (1512-1513, Siena, Santa Maria della Scala). The influence of Fra Bartolomeo, Filippino Lippi and Sodoma can be seen in these works, especially in the Triptych for the Trinity for the chapel’s altar.
His artistic style was already characterized by mannerism and anti-classical culture, taking inspiration from the works of Albrecht Durer and Piero di Cosimo, which was typical for Beccafumi’s works in the second decade of the 16th century, such as St. Paul in throne (1515, Siena, Museo dell’Opera del Duomo) the Stigmata of St. Catherine of Siena (1514, Siena, Pinanoteca) or the Holy Family (Munich, Alte Pinakothek, 1515-1525).
In 1517 he began working on the cartoons for the floor of the Siena cathedral and he dedicated his whole life to this work. In 1520 he traveled to Rome again, where he wanted to be informed on the latest news on art, particularly by Raphael and his workshop. Once he returned to Siena he was involved in other important commissions such as the decoration of the Sala del Concistori in Palazzo Pubblico (1529-1535) and the equipment for the arrival of Emperor Charles V in 1536. In this occasion Beccafumi met Prince Doria, who called him to Genoa around 1536-1537. In this period he returned to Rome for a brief stay.
Beccafumi was also an engraver and between 1547 and 1551 he made the eight bronze angels in the Siena cathedral, which were strongly linked to the sculptural tradition of the city.
Among his other important works were the frescoes for the Oratory of San Bernardino in Siena in 1518 with the Marriage of the Virgin and the Death of the Virgin, the Nativity (Siena, Pinacoteca Nazionale) and the panels for the Pisa cathedral between 1536 and 1539 with the Stories of Moses and the Evangelists.
Beccafumi died in Siena in 1551.