The Cambrai Madonna, also called the Notre-Dame de Grâce, produced around 1340, is a small Italo-Byzantine, possibly Sienese, replica of an Eleusa (Virgin of Tenderness) icon. The work on which it is based is believed to have originated in Tuscany c. 1300, and influenced a wide number of paintings from the following century as well as Florentine sculptures from the 1440–1450s. This version was in turn widely copied across Italy and northern Europe during the 14th and 15th centuries; Filippo Lippi's 1447 Enthroned Madonna and Child is a well known example.

When in 1450 the painting was brought to Cambrai, then part of the Holy Roman Empire ruled by the Dukes of Burgundy and now in France, it was believed an original by Saint Luke, patron saint of artists, for which Mary herself had sat as model. Thus it was treated as a relic; God bestowing miracles on those that travelled to view it.

The work is significant beyond its aesthetic value: it serves as a bridge between the Byzantine icon tradition and the Italian Quattrocento, and inspired the work of 15th-century Netherlandish artists. After the Ottoman Turks had conquered Constantinople, copies of the painting were commissioned in the Low Countries in support of Philip the Good's projected crusade, announced at the Feast of the Pheasant but never launched.

The painting is in tempera on a cedar panel, now backed by a modern board. It measures 35.5 x 26.5 cm, and is in generally good condition, with some local retouching. The initials "MR, DI, IHS, XRS" stand for the Latin Mater Dei, Jesu Christus, "Mother of God, Jesus Christ". It displays the gilded, decorated background typical of Byzantine devotional paintings, while Mary is dressed in a blue robe with gold lined edging. Christ, also typically of such Madonna and child works, possesses the body of an adult male rather that of an infant. He is burly, and far too large for a newborn child.

Mary is described by scholars as an Eleusa icon because of the tender manner in which the child is nestled against her cheek, setting the image as an intimate portrayal of the bond between mother and child. Her head is tilted towards her son and embraces his forehead and cheek almost as if in a kiss, while her arms warmly cradle him. He has one leg bent and another extended towards her, while his right arm is held upright and intimately holds her chin from below. This closeness and engagement of mother and child is a departure from Byzantine tradition, where they were often shown almost at arm's length, and was in tune with the ideals of the Italian Quattrocento.

The Italian origin of the work is shown in "the more subtle modeling of the faces, the volumetric aspect of the draperies with soft folds, the Latin inscriptions", and the style of the "elaborate punchwork of the haloes". A number of oddities in the different versions indicate that the many Italian versions came from a single source; primarily the closeness of the two figures' faces, their seeming embrace, as well as the unusual concentration of the child's facial features in a small portion of his head, which gives him an unusually long forehead.

The Cambrai Madonna was acquired by Jean Allarmet Cardinal of Brogny (d. 1426), who gave it to his secretary Fursy de Bruille, a canon of the Cambrai cathedral chapter, in Rome in 1440. De Bruille brought it to Cambrai, accepting its provenance as a work painted by Saint Luke, and in 1450 presented it to the Old Cambrai Cathedral, where it was installed with great ceremony in its Chapel of the Holy Trinity the following year on August 13, the eve of the Feast of the Assumption. Almost immediately it became the object of fervent pilgrimage, reflecting a contemporary appetite for new types of devotional imagery. A confraternity was established in 1453 for the "care and veneration" of the relic, which from 1455 was carried in procession through the town on the Feast of the Assumption (August 15).