fly into pisa and take train to florence or fly into rome and take plane to

Why not just fly directly to Florence? and then home from Rome. I am surprised that Pisa has a direct flight from the US. Since you are at the airport the easiest way would be into Rome and on to Florence.

Delta flies from New York directly into Pisa, and the one hour regional train ride is easy to downtown Florence. To fly into Florence, you'll go through one of the large European gateway airports, as there are no direct flights into Florence from North America. Regional trains in Italy do not accept reservations.
Flying home from Rome FCO is easy, as American Airlines has direct flights and Delta flies the route seasonally into New York JFK.

Flying into Pisa is just fine to get to Florence. Pisa is one of 4 cities in Italy with a train station in the airport. You most likely will be on two different Regionale trains for the trip to Florence. From the airport, its a 5-minute train ride to Pisa Centrale where you will change to a Regionale train to Florence. You won't be able to buy these tickets online from Trenitalia but don't worry. You can easily buy at the airport. Trip takes 60-75 mins depending on the run. Fare is 7.80Euro. Also note that when you buy the Regionale tickets in Italy, they are good for 60 days. They are not train or travel time specific. This is completely different from the higher-speed trains. No seat reservations permitted. Just validate your ticket before you board the train. Note also, that not having to catch the next train at Pisa Centrale, which you may wish to do, you can store your luggage in the very nice staffed left luggage facility in the train station and go visit the leaning tower. Once you have seen the tower, you can retrieve your luggage, validate your second ticket and catch the next Regionale train to Florence.

Caroline, You could also look at a flight directly to Florence, but as David mentioned you'll have to transit through one of the major hub airports. I'll be flying that route in a few months, and will be going through Frankfurt. If you decide to fly into Rome / FCO, it would probably be quicker to take the Leonardo Express to Termini and then Freccia train to Florence. While the flight time between Rome and Florence may be quick, there will also be waiting / layover times, security and all the usual airport hassles. Happy travels!

In your situation, use http://www.kayak.com, and choose "multi city" rather than "one way" or "round trip. For your first segment, put in NYC to Florence, and check "include nearby airports." For your second segment, put in FCO to NYC. See what comes up. That way, you can see if the JFK to Pisa flight is available for your dates (I don't think it's daily, and I'm almost positive it's seasonal), or if it would be cheaper to use a 1-stop flight to FLR. You can also fly from NYC to Bologna with one change; Bologna is also only an hour from Florence, so that's a good option if it's much cheaper than the other two airports. Finally, compare this price of these options to a straight round trip to Rome. You would then take the Leonardo Express to Roma Termini, and a train from Termini to Florence (so you have to account for the price of these trains, too). It's not as convenient as Florence, Pisa, or Bologna, but since you can get a nonstop, it might be worth it if you can save money.

I was curious too, so I checked on Orbitz and Delta. I do not see any NYC-PSA nonstops, the Delta shows a direct from JFK with a stop at CDG. However, Orbitz did show some FANTASTIC prices for round trip JFK-PSA for certain days dep mid May ret early June. Use "flexible dates" function to find them. These can't last.

Your options for Florence are: Option 1: Depart from: JFK/EWR Transit through: FRA or MUC (Lufthansa/United) or CDG (AirFrance/Delta) or AMS (Delta/KLM/Alitalia) Arrive to: FLR Option 2: Depart from: JFK Arrive to: PSA (Delta)
Train from PSA to Florence (see above comments). The non-stop flight JFK-PSA with Delta (option 2) operates only from June to August, 4 days a week. So if you go in May, that option is not available.

If necessary, the train b/n Roma Termini and Firenze SMN is around 1h30m, on top of getting from FCO to Roma Termini. So, it's perfectly doable if that's how things shake out for you (for example, IF you can save a few hundreds of $$$ to fly into FCO/Roma it might be worth it to you - that could pay for several more nights in Europe!). This is just an option...But direct to Pisa would be best (even if it's a little more $$$) because you could go directly to Firenze.

Simple: Fly directly into Pisa, take regional train to Florence as Larry describes above (reservation not necessary, comparable to the subway), fly out of Rome. Done.

I've always flown into Florence, via a major European hub. I find that much easier than dealing a train immediately after a trans-Atlantic flight. It's always been an easy connection to catch the flight into Florence.