The sitter was the second son of Cosimo I de' Medici (1519–1574) and Eleonora of Toledo (1522–1562), and was made a cardinal at age 17 on 31 January 1560, and Archbishop of Pisa the following year. Although Vasari mentions 'un ritratto di don Giovanni cardinale de'Medici figliulo del duca Cosimo' commissioned from Bronzino for 'reina Giovanna', the future grand duchess of Florence, no autograph prototype of this composition survives. The best known is probably the miniature (oil on copper, 17 x 12.5 cm.) today in the Uffizi, Florence (inv. 1890, no. 850), which originally formed part of a set of small-scale portraits of members of the Medici family, now assigned to the workshop of Bronzino.
A half-length version, attributed to Bronzino, was offered Rome, Christie's, 6 December 2001, lot 294 and a workshop version, depicted in bust-length, was sold London, Sotheby's, 6 July 1994, lot 226.