Of Leonardo da Vinci's works, the Mona Lisa is the only portrait whose authenticity has never been seriously questioned, and one of four works – the others being Saint Jerome in the Wilderness, Adoration of the Magi and The Last Supper – whose attribution has avoided controversy.

Leonardo had begun working on a portrait of Lisa del Giocondo, the model of the Mona Lisa, by October 1503. It is believed by some that the Mona Lisa was begun in 1503 or 1504 in Florence. Although the Louvre states that it was "doubtless painted between 1503 and 1506", art historian Martin Kemp says that there are some difficulties in confirming the dates with certainty. Alessandro Vezzosi believes that the painting is characteristic of Leonardo's style in the final years of his life, post-1513. Other academics argue that, given the historical documentation, Leonardo would have painted the work from 1513. According to Vasari, "after he had lingered over it four years, he left it unfinished".

In 1516, Leonardo was invited by King Francis I to work at the Clos Lucé near the Château d'Amboise; it is believed that he took the Mona Lisa with him and continued to work on it after he moved to France. Art historian Carmen C. Bambach has concluded that Leonardo probably continued refining the work until 1516 or 1517. Leonardo's right hand was paralytic c. 1517, which may indicate why he left the Mona Lisa unfinished.

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