Francesco Gattilusio gained the favor of Byzantine Emperor John V Palaiologos by helping him oust a rival to the throne, John VI Kantakouzenos, in 1354. As reward, Gattilusio was given lordship of the island of Lesbos (and its stronghold, Mytilene) from July 1355, as well as the hand in marriage of the emperor's sister, Maria. The Gattilusi possessions grew to include, among others, the islands of Imbros, Samothrace, Lemnos and Thasos, and the land city of Aenos (modern Enez in Turkey). From this position, they were heavily involved in the mining and marketing of alum, useful in textile production and a profitable trade controlled by the Genoese.
After the Fall of Constantinople in 1453, the Gattilusi briefly retained control of their possessions under Ottoman suzerainty, but were forced out within a few years. In 1456, the Ottomans appointed a native Greek historian, Michael Critobulus, as governor of Imbros, and likewise removed the Gattilusi from power in the remainder of their possessions, with the exception of Lesbos, which they were permitted to retain in return for an annual payment of 4,000 gold pieces. The lord of Lesbos, Domenico Gattilusio, was murdered and briefly succeeded by his brother Niccolò, before an Ottoman fleet captured the island in September 1462, sending Niccolò as prisoner to Constantinople (where he was later executed) and putting an end to the family's power.
Archaeological excavations in the castle of Mytilene since 1984 by the University of British Columbia under the direction of Caroline and Hector Williams have uncovered the burial chapel of the Gattilusi and a few graves that probably belonged to dependents of the family. The building was converted into a mosque after the Ottoman capture of Mytilene in 1462. The Canadian excavations have also added a considerable number of Gattilusi coins to the known corpus.
According to research by William Addams Reitwiesner published in 1995, the descendants of the Gattilusio dynasty (and therefore of the Palaiologos dynasty through princess Maria) include Donatien Alphonse François, Marquis de Sade (14th generation), Rainier III, Prince of Monaco (22nd generation), Otto von Habsburg, Crown Prince of Austria-Hungary (22nd generation), and Brooke Shields (23rd generation).
Lords of Lesbos
- Francesco I Gattilusio (1355–1384)
- Francesco II Gattilusio (1384–1404)
- Jacopo Gattilusio (1404–1428)
- Dorino I Gattilusio (1428–1455)
- Domenico Gattilusio (1455–1458)
- Niccolò Gattilusio (1458–1462)
Lords of Ainos
- Setton, vol. I, p. 225
- Setton, vol. II, p. 188
- Setton, vol. II, p. 239
- Setton, vol. II, p. 238
- William Addams Reitwiesner: "The Lesbian ancestors of Prince Rainier of Monaco, Dr. Otto von Habsburg, Brooke Shields and the Marquis de Sade" (1995)
- Kenneth M. Setton (1976). The Papacy and the Levant, 1204-1571: Volume I, The Thirteenth and Fourteenth Centuries. American Philosophical Society. ISBN 0-87169-114-0.
- Kenneth M. Setton (1978). The Papacy and the Levant, 1204-1571: Volume II, The Fifteenth Century. American Philosophical Society. ISBN 0-87169-127-2.