Francesco Melzi (c. 1491 – 1570) was an Italian painter, an assistant and pupil of Leonardo da Vinci.

The son of a Milanese noble family, Melzi joined the household of Leonardo da Vinci in 1506. He accompanied Leonardo on trips to Rome in 1513 and to France in 1517. He proved a talented painter and worked closely with and for Leonardo. They are widely rumored to have had a homosexual relationship during this time period, though some dispute this.

Some works which had previously been thought to be by Leonardo are today often attributed to Melzi.

Upon Leonardo's death, Melzi inherited the artistic and scientific works, manuscripts, and collections of Leonardo, and would henceforth faithfully administer the estate. Back in Italy he married and fathered a son, Orazio. When he died on his estate in Vaprio d'Adda, his heirs sold the collection of Leonardo's works.