Niccolo Gattilusio was the last Prince of Lesbos (1458-1462). A younger son of Prince Dorino, he desposed his elder brother Prince Domenico, threw him in prison, and had him strangled. Sultan Mehmed II used this crime as his pretext to invade Lesbos. In truth he was angry with Niccolo for the latter's sponsorship of Catalan pirates in the region.

After the Turks almost completely demolished the capitol city, Mytilini, and slaughtered many of the inhabitants, Niccolo surrended. He was carried off to Constantinople as a captive, along with most of his family. There he converted to Islam and was briefly released. His sister Maria Gattilusio (widow of Alexander, a brother of David of Trebizond), who was called the most beautiful woman of her day, disappeared into the sultan's harem. Her son Alexios became a page, but seems to have been beheaded not long afterwards.

Then Mehmed II discovered that a favorite page of his, who had fled from him some time before, had become Christian and was included among the retinue of Prince Niccolo. This final indignity seems to have hastened Niccolo's death sentence. He was strangled to death with a bowstring.