The commercial and cultural rivalry of Genoa and Venice was played out through the thirteenth century. The Republic of Venice played a significant role in the Fourth Crusade, diverting "Latin" energies to the ruin of its former patron and present trading rival, Constantinople. As a result, Venetian support of the newly established Latin Empire meant that Venetian trading rights were enforced, and Venice gained control of a large portion of the commerce of the eastern Mediterranean.

In order to regain control of the commerce, the Republic of Genoa allied with Michael VIII Palaiologos, emperor of Nicaea, who wanted to restore the Byzantine Empire by recapturing Constantinople. In March 1261 the treaty of the alliance was signed in Nymphaeum. On July 25, 1261, Nicaean troops under Alexios Strategopoulos recaptured Constantinople.

As a result, the balance of favour tipped toward Genoa, which was granted free trade rights in the Nicene Empire. Besides the control of commerce in the hands of Genoese merchants, Genoa received ports and way stations in many islands and settlements in the Aegean Sea. The islands of Chios and Lesbos became commercial stations of Genoa as well as the city of Smyrna (Izmir).