The Jewish people were among the first Europeans to arrive in the New World after Columbus's voyage. In fact, there has been speculation that Columbus was of Jewish heritage or possibly even a marrano, though nothing has ever been conclusively proven. The last name Colombo (Columbus's name in Italian) was common among Jews in Italy. And although he was a legal citizen of Genoa, he was fluent in Spanish and apparently didn't know how to write in Italian, perhaps because he was a son or grandson of Spanish Jews.

Columbus relied upon two Jews in planning his voyage—Abraham Zacuto, who drew the tables, and Joseph Vecinho, who had perfected the instruments which Columbus used to navigate. What is more, the first member of Columbus's expedition to set foot in the New World was his interpreter, Luis de Torres, a Jew who had been hastily baptized before the voyage.

Just four days before Christopher Columbus set sail to discover a new world that would become a haven for millions of Jews, the last group of Jews left Spain in compliance with the Order of Expulsion.