Potentially the most exciting outcome of Seracini’s researches into the original architecture of the Hall of Five Hundred in the Palazzo Vecchio in Florence, would be the discovery of a large mural by Leonardo that was last seen in the first half of the sixteenth century, the Battle of Anghiari. This was a painting thought to be three times the size of another great work, The Last Supper. Following Vasari's renovation of the Palazzo Vecchio in 1563, the Battle of Anghiari disappeared without trace.

According to Kenneth Clark, writing in Leonardo da Vinci, "The Battle of Anghiari was, in some ways, Leonardo's most important commission. At the height of his powers he was given a subject ideally suited to his genius. Michelangelo, his sole artistic equal, was executing a drawing in the same hall. Judging from sketches which remain, Leonardo was given the opportunity to display his unique skills". The art historian Carlo Pedretti has argued that the composition of the Battle of Anghiari afforded Leonardo "the opportunity of a total reconsideration of the human figure, from structure to surface modeling, and from ideal proportions to expression".

"These battle cartoons of Leonardo and Michelangelo", emphasizes Kenneth Clark, "are the turning point of the Renaissance… they initiate the two styles which sixteenth century painting was to develop – the Baroque and the Classical."

Michelangelo's work was never transferred from cartoon to wall, but Leonardo's was and there are good reasons to believe that the Battle of Anghiari still exists. The rulers of Florence, the Medicis, had certainly left it on public display for several decades after it was painted. When the Hall became a dormitory for their mercenary troops during a period of unrest, they even paid a carpenter to build a wooden frame designed to protect the mural from the soldiers. If the Battle of Anghiari is not visible today, some experts believe, it is because it is hidden inside one of the long walls, which was adjusted in 1512 to make the Hall a rectangle. The wall was thickened and straightened as part of a wider renovation, designed to allow the addition of six battle scenes and epic monuments celebrating the glory of the Medici family. Also, no documents mention anyone's intention to destroy Leonardo's work.

Most importantly, perhaps, the artist who contributed the new works to the Hall, Giorgio Vasari, has left us both painted evidence and a further clue to the continued presence of the Battle of Anghiari. He painted a battle between men on horseback which is very similar to the one painted by Leonardo. Vasari, moreover, placed it directly in front of the place in which the Battle of Anghiari is likely to be. Vasari also left a mysterious inscription on the eastern wall, in the top part of his own battle scene. Written on one of the soldiers' banners is a simple but intriguing phrase:

"Cerca trova - HE WHO SEEKS, FINDS".