Although Palestrina's Motets constitute an important contribution to the sacred repertoire, it is his Masses, above all, with their enormous variety and consummate polyphonic skill, which have secured him an unrivalled reputation. Although few can be dated with any certainty they fall into three distinct stylistic categories: early works, often with secular titles; middle-period works which are marked by a new dignity and conciseness, even austerity, in response to the requirements of the Council of Trent of 1562; and late works which are characterised by richness and melodic beauty. Some 43 Masses were printed in six volumes during his lifetime; Palestrina's son organised the publication of a further seven volumes soon after his death in 1594. The Missa Iste Confessor, evidently a late work, was published in Rome in 1590 and a second edition was issued a year later in Venice.

Palestrina's most favoured compositional method, employed in 53 of his Masses, was the 'parody' technique, drawing on pre-existing polyphonic works. However the Iste Confessor Mass is one of his 35 'paraphrase' masses based on a plainsong melody - here a hymn from the Vespers for the Commemoration of a Confessor (see below). The melodic suavity of the Mass, imbuing the texture with richness and beauty, reveals the composer at the height of his powers. The plainsong motifs are incorporated to an extraordinary degree - overtly in no fewer than two-thirds of the bars with traces of them in almost all the remaining ones.

Palestrina also drew on the Iste Confessor plainsong in a collection of hymn settings published in 1589, a year before the Mass. The five-stanza Hymn comprises three polyphonic verses which alternate with the plainsong.