[4] Unusually for a southern Italian artist of the Renaissance, his work proved influential on painters in northern Italy, especially in Venice.

Antonello was born at Messina around 1429–1431, to Garita (Margherita) and Giovanni de Antonio Mazonus, a sculptor who trained him early on.

According to a letter written in 1524 by the Neapolitan humanist Pietro Summonte, in about 1450 Antonello was a pupil of the painter Niccolò Colantonio in Naples.

In that year, Antonello painted the so-called Salting Madonna, in which standard iconography and Flemish style are combined with a greater attention in the volumetric proportions of the figures, probably indicating a knowledge of works by Piero della Francesca.

Also from around 1460 are two small panels depicting Abraham Served by the Angels and St. Jerome Penitent now in the Museo Nazionale della Magna Grecia in Reggio Calabria.

They follow a Netherlandish model, the subject being shown bust-length, against a dark background, full face or in three-quarter view,[11] while most previous Italian painters had adopted the medal-style profile pose for individual portraits.

His works of this period begin to show a greater attention to the human figure, regarding both anatomy and expressivity, indicating the influence of Piero della Francesca and Giovanni Bellini.

The San Cassiano Altarpiece was especially influential on Venetian painters, as it was one of the first of the large compositions in the sacra conversazione format which was perfected by Giovanni Bellini (Antonello's surviving work in Vienna is only a fragment of a much larger original).

[11] Works from near the end of his life include the famous Virgin Annunciate, now in the Palazzo Abatellis in Palermo, and the San Gregorio Polyptych.