This article examines women’s speech in the Renaissance as it is represented in the frescoes painted by Domenico Ghirlandaio between 1486 and 1490 in the Tornabuoni Family Chapel in the Dominican church of Santa Maria Novella in Florence. It is argued that the upper-class Florentine women who appear in these frescoes perform as exemplars of desired female speech behavior. The representation of speech in these frescoes is considered relative to Florentine notions about speech found in texts by one of the most influential men in Renaissance Florence, the Dominican Archbishop of Florence Antonino Pierozzi (1389–1459, archbishop 1446–1459, later canonized as St Antoninus). These texts include chapters in Antoninus’s Summa theologica (c. 1440–1454) on ‘Speech and its Multiple Vices’ and ‘On the Diverse Vices of Women, Alphabetized’, which address the negative aspects of speech. Also considered are the recommendations for self-regulation of women’s speech in the Opera a ben vivere, written by Antoninus in c. 1454 for Dianora and Lucrezia Tornabuoni, both of whom may be represented in the Tornabuoni Chapel frescoes. In particular, this text stresses the sins of idle talk (i.e. gossip and tale-telling) and talking too much, two negative types of speech that were (and still often are) associated with women. In addition to the authoritative male voice of Antoninus, women’s speech in the Tornabuoni frescoes is interpreted in relation the Storie Sacre written by Lucrezia Tornabuoni in the 1460s or 1470s, which provide some alternative types of profitable speech for women, other than what is recommended by Antoninus and modeled in the frescoes.