Rental Cars and Train to Monterosso Al Mare

You could return the car in Florence and take the train from there, approx. 2 1/2 hours. Or, drive to La Spezia, (approx.1 hr 45 min) which is just south of Cinque Terre, return the car, and take a short train ride into Monterosso.

Most of us here use the following consolidators (now part of the same corporate umbrella):
www.autoeurope.com
www.kemwel.com
They work primarily with Avis Budget, Europcar, Hertz, and others, basically the largest car rental companies in Italy.
Your pick up location I presume will be Fiumicino airport.
The drop off location closest to the Cinque Terre is the city of La Spezia.

I'd like also to mention that if you plan to visit Rome before heading to Tuscany, it is better to visit Rome without a car and rent the vehicle in the city at the end of your trip.

If while in Tuscany you are visiting Florence, find accommodations outside the city center or, even better, outside Florence. When you visit the city, park outside the city walls in one of the parking lots.

Same is true for most towns, big and small. Access to the historical centers is prohibited to vehicles without resident permit. The entrance to the areas closed to traffic is signaled by a ZTL (Zona Traffico Limitato) sign. These restrictions are enforced by cameras, therefore don't assume you can enter just because you see no cops around. Same is true for speeding:
http://www.slowtrav.com/italy/driving/traffic_cameras_speeding.htm

Yes thanks so much for your response. Our previous trips we only used public transporation. We have been to Rome twice and loved it but will not be doing any activities in Rome this trip except flying in to the city. We have been to Florence and do not plan to visit while we are touring Tuscany. We are flying out of Florence and may spend a day before going home but will not have the car.
Is there advice about how far in advance to secure the rental car?

You don't specify your time of travel.
I generally fly to Italy at the end of June or very beginning of July every year.
My flight destination is nearly always Florence (or Rome/Milan occasionally).
I generally book the car with the consolidators above about one month or less before my expected travel date. But you can do so as early or as late as you like, whenever you buy the plane tickets and know the exact dates of your flight.
When you book with those consolidators you must prepay the car rental, but if you need to cancel you are entitled to a full refund as long as you cancel before 48 hours from your rental start date.
Car rental prices tend to jump up considerably after July 1 until Aug 31, therefore if you can travel before (or after) that time period (or at least pick up the car before June 30 or after Sept 1) you can save quite a bit of money.

Thank you Roberto. We are going on the first week of May.