The icon features the child Jesus fleeing into his Mother's protective arms as the Archangels Michael and Gabriel show Him the instruments of crucifixion. The Greek letters spell out the first letters of Mary and Jesus' names.
The icon arrived in Rome in the 15th century after a merchant who had heard about a miraculous image on the island of Crete went to the island and stole it. When he arrived in Rome with the icon among his wares, he fell very ill. As he lay dying, he ordered that a friend place the icon in a church, perhaps hoping that it would alleviate his suffering. The friend took the icon to his own home, where his wife hung it in their bedroom.
The Virgin evidently was not pleased with this arrangement, and several times appeared to the man and told him that she wished for her image to be placed in a church. The man, despite the miraculous visitation, was not moved to relinquish control of the image. The Blessed Virgin next appeared to the man's daughter and asked that the icon be enshrined in a church between the two very large churches of St. Mary Major and St. John Lateran. The daughter communicated this to her father and he relented, and so the icon was enshrined in 1499 in St. Matthew's, the church that lies between the two larger edifices.