The specific identity of the sitters in this, Titian’s largest group portrait, is disputed, but the man in the centre is most likely Andrea Vendramin (1481–1547), while the one on his right is his brother Gabriel Vendramin (1484–1552), a significant collector of works of art. The boys are the former’s seven sons. The reliquary of the True Cross on the altar still exists in the Scuola di S. Giovanni Evangelista in Venice. It was presented to an earlier Andrea Vendramin, Guardian of the Scuola, on behalf of this confraternity in 1369. On one occasion he is said to have rescued it from a canal.
The painting was surely made for a specific site in the family’s Venetian palazzo. During execution, however, it was cut down on the left, probably because the patron changed the intended location. This accounts for the slightly awkward accommodation of the three boys at far left, who were surely painted by the artist's workshop. The two boys on the far right were probably also painted by an assistant: they are markedly drier of execution than the freely and luminously painted boy holding a puppy. Parts of the paint surface have become transparent with time, revealing to the naked eye Titian’s vigorous preparatory underdrawing of Gabriele.