We first witness the self-portrait used as a signature in ancient Egypt. It is difficult to say for sure whether some of the sculptures recovered from that period are definitely self-portraits, but because we know that portraiture was reserved for the rich and powerful, it is generally assumed that works containing less decorated individuals were portraits of the artists themselves. The self-portrait as a signature reappeared strongly during the Middle Ages and the Renaissance period. Architects from the great cathedrals would sometimes carve images of themselves in less noticeable parts of their finished pieces. Two well known examples are the cathedrals at Santiago di Compestello and Prague.

During the Renaissance period sculptor Lorenzo Ghiberti is said to have chiseled a self portrait, as early as 1401, into the frame surrounding the set of bronze doors created for the Florence Baptistry. Jan van Eyck is thought to be present in a small detail from his famous masterpiece, The Ghent Altarpiece, completed in 1432. But his most influential painting of the period, Wedding Portrait from 1434 employed a quite unique use of the self-portrait. A young couple stands facing the viewer while exchanging their wedding vows. A mirror behind the couple, in the center of the painting, reveals Jan Van Eyck's presence in the room. His inscription above the mirror reads "Johannes de eyck fuit hic" or "Jan van Eyck was here."

Roger van der Weyden, another great master Flemish painter is claimed to have been his own model, portraying St. Luke in St. Luke Painting the Virgin. He is also given credit for being one of the earliest portrait artists to "tell us more about the inner life of his sitters, less about their outward appearance."