How to drive from Cortina D'Ampezzo in the Dolomites to Cinque Terre and returning the rental car.

Milan is a major hub, so I would look at that.

Bolzano would be easy. Avis and Hertz are not too far from the train station although you very well may want a taxi it will be a short ride. Even the airport is not terribly distant. Then take the train to Milan via Verona and on to the Cinque Terre.

You could also return in Verona but the downtown location is difficult (to me) close to the ZTL and easy to make that mistake. The Verona airport is a bit out of town so a longer taxi ride to the train.

There is also Florence Airport, then take the new tram to S.M.N. station with frequent regional trains to Pisa and the Cinque Terre.

For our trip around the Dolomites and Julian Alps we rented in Verona and returned the car in Padua. Pick a good train hub and go for it..... Drive carefully, downtown Italian cities have lots of one ways and bus/tram lines that are not to be crossed.

From Cortina, the simplest thing to do would be to return the car in Padua. All the major rental outfits have offices near the rail station, all outside of any ZTL’s. Frequent train service to Milan for your journey to the CT. You could also return the car in Venice but to me Padua is more “user friendly.”

Direct IC trains from Milano to Monterosso call at Pavia and Voghera. If you could return the car There you would avoid driving in Milan, a city blessed by ZTLs and congestion charge areas. Milan’s Rogoredo station would be the second best option, easier than Centrale.

To get either to Florence or to La Spezia you should drive through the Apennines. Either along the new section of A1 or on the A15. Both are divided mountain motorways, the drive is relatively easy but boring. Those passengers who don't like tunnels and viaducts find the new A1 a little nerve wracking.

Return the car in La Spezia. The drive is quite easy and pretty and from the Verona area it's only 3 hours. Since you have to drive out of the mountains to the pianura no matter what, why bother with a transfer and the train trip? On the way you could stop and see a pretty small town like Mantua, Castell'Arquato, or Pontremoli. There's a map of LaSpezia rental locations in this article: https://www.apathtolunch.com/2015/11/where-to-rent-car-from-cinque-terre-la.html

Thank you all for your suggestions.

Mike, what exact route would you suggest for the drive from Cortina D'Ampezzo to Spezia. ( We have not been in Italy in a very long time so our memories of driving in Italy are very vague.) We are strongly considering your suggestion.

To drive from Cortina to La Spezia, I would stick to the Autostrade (toll highways) : South to Padua, West to Verona, South again towards Modena, then West towards Parma, and finally south to La Spezia.
Looks like you can drive straight from Mantua to Parma to cut a corner, on a two lane road: never done it, not sure it saves time.

Yes, balzo has described the best route. Google Maps may suggest a slightly shorter route past Bologna, but that often has too much traffic in my opinion.