first time to Italy, seeking itinerary advice

Vernazza in 5 Terre.

Rent a car and stay somewhere near San Gimignano. Suggest Villa Arnilu or Agritourismo Niccolai by the day. Day trips to Florence and Siena are easy frim there. Train to.Florence and car to Siena. Go to Volterra is easy and Pisa is doable.

You can also go to the east of the SiFi autostrada and hot some of Chianti, perhaps Panzano.

Venice? You should work it in.

Actually, so far you're doing it all right, and congrats on your anniversary as well as eschewing a tour and doing it yourself. Many treasures await you!

Different strokes, but I'm doing 4 Rome, 4 Florence, 3 Cinque Terre. Take trains in between bases--90 minutes Rome/Florence, under 3 hours Florence/La Spezia (including transfers), 3 hours La Spezia/Milan. Explore Rome (I'll be doing it for six nights shortly) by staying in the historic district and walking, eating, exploring. Same in Florence, staying within walking distance to the Santa Maria Novella train station for easy access for daytrips--Siena, Fiesole, Lucca, heck even Venice is only 2 hours each way. And you might be able to access some cycling out in the hills around Florence, maybe parlay that with some type of winery visit. Not familiar with the C.T.

Enjoy your planning!

To determine your number-of-days-allotment, make lists of what you wish to do in each place (including relax). Of course it would take decades to see everything in Rome, so just choose what is most important for you in each place. You could potentially stay in Rome, Florence, somewhere smaller in Tuscany, and CT, but most would probably not change bases that many times.
Trains are super easy. For CT, the villages are tiny and well connected, so I would choose based on accommodation. Try to avoid CT on the weekend for less traffic on the trails (assuming you will be hiking).
I would certainly hire a driver if wine tasting is on the agenda.

Sounds like a great trip!

We always rented a car, but it should be easy to travel by train from and to all the locations you've mentioned.

You could either rent a car or take a wine tasting tour of Tuscany, it's a matter of how you like to do things. There are some good tours out of Florence which may be the easier choice for you. Siena would not be the same as traveling through the countryside. I don't think you have time to do both, it would eat up two full days.

There are festivals in Italy in September. Be sure to check to see if your schedule puts you nearby.

When in Rome and Florence, consider taking Walks of Italy tours. We took two in Florence and one in Rome. Some offer special access and they provide tickets that let you skip the line. Our guides were very knowledgeable and we felt they were worth the money.

I'd plan on three days in Rome, three days in Florence, one day in Tuscany, two days in Cinque Terre and the rest in Milan.

Day 1 - arrive Rome
Day 2 - Rome
Day 3 - Rome
Day 4 - morning train to Florence, afternoon Florence
Day 5 - Florence
Day 6 - Tuscany
Day 7 - Florence
Day 8 - morning travel to Cinque Terre
Day 9 - Cinque Terre
Day 10 - morning travel to Milan
Day 11 - Milan
Day 12 - Milan
Day 13 - travel home

The above is just a suggestion, but it is to show that 13 days sounds like a lot, but really isn't that much time.

Your first day is your zombie day (jetlag, lack of sleep), so don't expect to accomplish much that day other than some walking around outdoors. For that reason, I'd recommend 4 nights in Rome, your first stop. Alternatively, you could plan a late train from Rome to Florence after 3 nights in Rome, to give you some extra time in the (much) larger city.

Beyond that, it's sort of a matter of what interests you most. I agree that trying to squeeze in both a day in Siena and a day in the Tuscan countryside may not be the best idea; however, the Siena day-trip is something that can be decided on the spot, based on how much you're enjoying Florence itself, so you might keep that open.

The Duomo in Milan is a very worthwhile sightseeing stop if you get to the city early enough. Should you wish to see The Last Supper, you should investigate the ticket situation, because that is a limited-access sight that sells out.

Congrats on your upcoming anniversary; there's no better place to spend it than in Italy!

The schedule in the post just before this looks pretty good to me but I'd take 2 days off Milan and add them to Rome and the CT.

Day 1 - arrive Rome
Day 2 - Rome
Day 3 - Rome
Day 4 - Rome
Day 5 - morning train to Florence, afternoon Florence
Day 6 - Florence
Day 7 - Tuscany day trip
Day 8 - Florence
Day 9 - late morning travel to Cinque Terre
Day 10 - Cinque Terre
Day 11 - Cinque Terre
Day 12 - Milan
Day 13 - travel home

This itinerary is best done by train as cars are of no use at all in the cities. You could rent a car for an exploration day in Tuscany (without too much wine tasting!) or just take the bus to Siena. Rome really demands at least 3 full days - more is better - as there's so much to see, and with an interest and history and art, Florence deserves its fair share too (the art, the art, the art!!!)

You could take one day off the CT and add it to Florence for another day trip, if you wished?

LOL, I'd be WAY too chicken to try and navigate a bike on the street of Rome or Florence, and CT is a lousy place for two wheeling, IMHO. Villa Borghese park in Rome, however is very large and I know there's a bike rental place there. Another idea would be to sign up for a mountain bike tour of, say, the Appia Antica (Rome.) They rent bikes out there too but because the 'road' goes quite some distance out, having mechanical support is a plus should you have a breakdown.

We all have our favorite village for staying in the CT, and mine would be Monterosso as it's the largest and the less-easily overrun...and the Cinque Terre will still be overrun in September. It also has the largest number of restaurants and whatnot. Tiny Corniglia is lovely but it also must be reached via a little bus or a loooooong switchback stairway from its train station.

Sightseeing on your own is easily and economically done without tours as long as you pre-purchase timed-entry tickets to the biggies to avoid standing in line. Some attractions - such as Galleria Borghese in Rome - require reservations. We can point you in the right direction for what does and doesn't need taking care of in advance and how to do that if you share your wish list?

Please look at the maninseat61.com for advice on trains. Get a good guidebook and read through that. It's not that difficult to put this trip together on your own, but to make the most of it, a good guidebook is very helpful.

Sounds like a good plan. I would try to book a day trip in Tuscany. A drive thru the country with stop at vineyard and quick highlights of Siena is a nice full day trip.
Since you are leaving from Milan, a day there is worth the time if schedule permits. (One person's opinion is that a day or two in CT is enough). The central area around the Duomo and Galleria in Milan is the main place for limited time. The tickets to only the Last Supper seem to be impossible. You get stuck with a several hour bus tour that includes La Scalia, the castle near the Duomo and the Last Supper. The painting is extraordinary, but you spend a lot of tour time for your 20 minutes at the dinner table.

Wow, thank you all so much, this is the first time I've used this forum and I'm so grateful for the great advice and feedback from experienced Italy travelers! I have a feeling I am going to want to return again and again. Great suggestions on itinerary planning and other activities to consider and enjoy. Thank you again!