The double-sided icon at left depicts two of the most influential images in Byzantine art. On the front, the Virgin Hodegetria (“she who points the way”) gestures toward the Christ child as the path to salvation. The image derives ultimately from a venerated model that was the subject of legend: it was believed to have been painted from life by Saint Luke and brought to Constantinople from Jerusalem in the fifth century. Pilgrims flocked to the Monastery of the Hodegon to revere the original icon, which was paraded weekly through the streets of the capital. Widely copied, it is one of the most common types of images of the Virgin.

On the other side, below, the icon of Christ after the Crucifixion, laid out for burial with his arms at his sides, is the earliest known panel painting of the Man of Sorrows, a name taken from an Old Testament description of the Messiah: "He is despised and rejected of men, a man of sorrows, acquainted with grief (Isaiah 53:3)." Called Akra Tapaneiosis (Ultimate Humiliation) in the Greek Orthodox Church, the subject originated in Byzantium in the 11th century in response to liturgical changes and became widespread in the medieval West.

The Kastoria icon imbues the traditional Virgin Hodegetria with heightened emotion found also in hymns and sermons, especially after Iconoclasm. Her sorrowful expression and furrowed brow suggest that she foresees her son’s death. On Mary’s grief at the Crucifixion, the ninth-century bishop George of Nicomedia wrote,"Who will enumerate the arrows that penetrated her heart? Who will recount in words her pains that are beyond words?" His sermon served as the lesson on Good Friday when this icon was displayed during the church service commemorating Christ’s Crucifixion.