flying into Italy

All you can do is try different combinations. Milan comes up cheaper a lot for me, so you can fly into Milan, out of Rome, or vice versa. You also will want to look at direct flights from the US versus those that require a connection somewhere in Europe. You may save a few $$, but it takes a lot more time.

The major difference between the two airports is that Rome-FCO has flights to and from the U.S. The Amerigo Vesupucci airport in Florence has flights to and from other EU cities but not the U.S. It's a smaller airport and the very large planes do not fly in or out of there. If you fly out of Florence, they wil simply fly you to another EU city where you transfer to a larger plane home. Same with Marco Polo in Venice should you want to fly out of there. Pisa does have Delta out of Newark, N.J. but not many other U.S. airlines. Milan would be the closest airport to Rome with numerous U.S. flight connections. Secondly, Florence and Rome are only 1hr15min apart on the high-speed train. You're not really saving much. If Rome and Florence are the only places you intend to visit (including day trips), you can easily get back to Rome for a final night before flying out. If your travel plans will take you to cities beyond Northern Italy, you can fly Lufthansa, Swiss Air, Air France to their major airports in Germany, Switzerland and France and transfer into or out of Florence. For our experience, we have flown into Florence on Lufthansa via Frankfurt and out of Zurich on United. Lufthansa is a partner airline of United. It worked quite well.