One of the most famous artists of the Venetian school, Lorenzo Lotto was born in 1480 in Venice. Dated 1503, the first document about Lotto refers to him as the son of the "late Thomas of Venice" and states that his father was a painter in Treviso. Nothing is known about his apprenticeship, although a thorough understanding of contemporary Venetian painting is apparent in his earliest works. His first paintings include two altarpieces at the church of Santa Cristina, Treviso (1505) and Asolo Cathedral (1506) as well as several portraits and devotional paintings. Lotto left Treviso in 1506 and traveled to Recanati to begin work on the high altarpiece of the church of Saint Domenico, completed in 1508. His later work for other Dominican churches and his request in 1542 to be buried in a Dominican habit suggests a close association with the order. In 1508 he worked in Rome decorating the Vatican Palace. In 1509 Lotto was paid for work "in the upper rooms of pope"; exactly where and what he painted is unknown.

In May 1513 Lotto arrived in Bergamo to paint the high altarpieces in the Dominican church of Saint Stefano. Between 1521 and 1523 Lotto finished five other altarpieces in Bergamo. At the end of 1525 the artist arrived in Venice and remained there until 1532.

While in Venice he painted at least five altarpieces for churches in the Marches. After long periods in Bergamo and Venice, Lotto changed residence frequently during the last 24 years of his life. He returned to Venice in December 1545 and painted the altarpiece The Virgin and Child with Four Saints, which was finished in the following year.

Lotto's account book shows that it was becoming increasingly difficult for him to earn a living as a painter in Venice. He returned to the Marches in 1549. The final two years of his life Lotto spent as an oblate in Santa Casa of Loreto. During this time, he executed various decorations for the basilica of Santa Maria and other works in the Palazzo Apostolico.