The Gattilusio family [Francisco (1409-1426), Dorino (1426-1449), Domenico (1449), Niccolo (1462) rules the island, engaging in the trade of alum , olive oil, wax, minting coins and learns the greek language. There is a Latin bishop as well as the two orthodox bishops. The castles of Molyvos and Mytilene are expanded. This also seems to be the case for the others. The names of many settlements on the island which are inscribed on notarial deeds are identical to their present-day names (Eressos, Kalloni, Moria, Akrotiri, Petra, Parakoila, Chalikas, Thermi). Towers are scattered all over the countryside (Vrisa, Thermi, Sigri etc.).

The houses of the aristocracy the loggia and the Chancellery (where business deals are concluded) are located within the Castle walls.

In 1450 Murad orders Baltaoglu to destroy Kalloni and indeed he succeeds . Then the latter besieges Molyvos but fails..

Even today the family emblem is exists on the castles (double-headed eagle with a lamellar armour).