Car or Bus to Rome

Since you have the car, drop it in Rome. Termini is convenient and easily accessed.

You could also take the train from Siena after you drop off the car.

I generally drive to Rome either to Termini or Tiburtina stations, but some people are scared to drive in any place where there are more than 5 cars driving on the same road, so it depends if you are used to city driving. However, even if you are not comfortable driving in cities, there are numerous rental offices in Rome, away from the city center, that are easy to reach from the freeway exits. Tiburtina station is easy to reach from the Tangenziale Est/A24 and Termini is not much farther. Once you have decided which rental company to use, go to their website and check the location of all their offices in Rome, then choose one that looks easy to reach from the GRA or from the north.

Thank you all for your advise. It is very helpful! I'm feeling more confident in driving to Rome and dropping the car off there. I know it will save time and not require any backtracking.

Remember you can use Google Maps Streetview to take a look at the driving route before you go. That will help you see if there are any spots that might be confusing.

Yes, thank God for Google Maps!!

We used the Europcar rental location near the Vatican so we didn't have to drive into the main part if Rome. Also, it was the closest location to head north toward Tuscany. By the way, Pitigliano is amazing to see, and the natural hotsprings, cascadia Saturnia, which are about 15 miles north, are wonderful!