First visit to Italy, 3 weeks (leaving in 2 weeks)

With your sensitivity to mold, since it's your first time in Europe you really don't know how your body may react to different organisms. I'd recommend getting a laminated card in Italian from Select Wisely that explains your concern. See <<
https://www.selectwisely.com/ >> You can explain this ahead of time when you book your rooms, and having it written down in Italian should make it easier to avoid the management getting angry and trying to charge you for a full stay if you have to switch to a non-moldy hotel.

You'd probably also be better off choosing modern hotels in the mid- or higher price range, though of course that's no guarantee.

If you want to see Venice without staying in a hotel there, you could stay in a nearby town (such as Treviso or Padua) and go into Venice for a day.

I recommend borrowing a few nights from Rome and/or Florence and give them to Venice.
Make sure you give at least 3 nights each city. Since you seem to have an interest in smaller towns also, give at least an extra night to Rome, so that you can visit Orvieto, and some extra night(s) to Florence to take day trips to Tuscany.

The historical center of Venice has very old buildings which are near water, so you might want to stay in Venezia Mestre, in the mainland just across the bridge (less than 10 min to Venezia Santa Lucia station).

I have stayed at the hotel Triton a couple of years ago, in front of the Venezia Mestre station. It is modern hotel that is unlikely to have mold. From there it's also a quick taxi drive to the airport.

http://www.hoteltritonevenice.com

Thanks for the replies so far. I have actually been to Europe a few times. Last time I was 6 weeks in Switzerland and France. I agree that modern hotels seem better for mold, but that isn't actually true. In fact they often can be worse. I just stayed in a $3m recently remodeled condo in New York City and there was mold in the AC ducts. The most common sources of mold are leaks behind walls, and heating/AC ducts.

Anyway, my question is really focused around the itinerary, and I just wanted to explain that I don't want to spend 1-2 days each in a number of different hotels, and why I unfortunately need to stay with larger chains where I could be moved to a different room or hotel, or a hotel where I am allowed to cancel early.

Any other suggestions about my itinerary?

I like your itinerary, generally. As you are doing, I like to stay put longer and get to know an area better than running through it. As you are seeing the Amalfi Coast, I'd skip Cinque Terre...but I'm saying that never having been there and the more I hear about it, never wanting to go there. I love Florence. It is my favorite Italian city. From Florence you could also check out Milano, but you might find you want to stay in Florence more days. That's just me. It looks like a great trip! Wray

Other places in northern Italy that I especially like, which could be visited as side-trips:

Lucca: Eeasy side-trip from Florence, same day as Pisa; nearly everyone seems to prefer Lucca
Padova: Very near Venice, Scrovegni Chapel needs reservation
Vicenza: Palladian architecture, just a bit farther west of Venice
Ravenna: On a spur rail line east of Bologna, but absolutely worth as close to a full day as you can manage for the charming old town and the incredible mosaics

I've never been to Ferrara (just north of Bologna), but I really regret that, given the positive things several people have said about it.

Your plans seems pretty good, however:

1) The ferries may not be running to Amalfi Coast...depends on the weather. They were not running last October when I was there (trying again this year). Research private or semi private tours as a backup.

2) Yes stay in Sorrento as your base it is the easiest for first-timers. Yes, you can take a local train (Circumvesiviana) between Naples and Sorrento with a stop at Pompei Scavi station to go to Pompeii.

3) Capri is touristy but lovely. A private boat tour (half or full day) is best so you can swim and see the whole island.

4) Florence is wonderful but I would loose a day there and add one to your time in Amalfi or CT

5) You can take a day trip to Venice using the fast Freccia train from Florence. Take the train from S.M. Novella to Venecia S. Lucia which should take about 3 hours. Check train time on TrenItalia.com. I didn't notice mold in Venice but it is the start of the rain and flood season so if it is not a priority maybe you check the weather report and decide when/if to go.

6) How many people are staying? In Florence, I stayed at Ciao Hostel (shared bathroom and kitchen) but very nice and clean, no mold. In Venice, I stayed at Hotel Certosa, very nice close but not the main island. No mold.

7) Have you discovered Booking.com? You can book with a small deposit which allows you to have two reservations in the same town just in case.

I have encountered mold in ceilings and bathrooms from time to time, not pervasive, but if this is an issue for you, contact the hotel directly and let them know of your concern. The few times I saw mold in a room, I asked for a different room and got it. In a small hotel, this might not be possible.

If you do double-book rooms, you will probably be charged as a no-show for the place you don't stay at if you decide to stay in the first hotel you find; policies vary on cancelling because you reject the room and they have nothing else to offer.

Some corrections to mandy...'s advice:

Trenitalia shows trains from Firenze Santa Maria Novella to Venezia Santa Lucia taking 2 hours and 5 minutes, departures almost every hour.

Booking.com does not charge you a deposit; the property you reserve may, but this will be disclosed during the booking process.

Take care with booking.com. The cancellation cut-off can be 72 hours in advance and is rarely less than 24 hours (or perhaps it's one full calendar day?). I don't think it's ever possible to cancel on the planned day of arrival without losing at least one night's payment and possibly the full payment.

I use booking.com all the time and am not saying it is worse than any other hotel-reservation website. It's just that here in the US one can often cancel up until 3 PM or even 6 PM on the day of arrival.

Thanks. I've got so many great ideas, we're just going to Rome first and will play it by ear. We are leaving in 3 days and there's still availability at most of the hotels.

After watching more RS videos and reading his guidebook, I'm thinking something like this
5 days Rome Sep 21-26

3 days Amalfi Sep 26-29 Pompeii on the way to Sorrento, then to Positano and Amalfi, maybe Capri
5 days Florence with day trips Sep 29-Oct 4 Or maybe we'll decide to get a car and stay in a hill town. Either way we'll do a bunch of hill towns
3 days Cinque Terra Oct 4-7 Small hotels here so might skip or cut short and go to Padova early
5 days Padova Oct 7-12 Realized there are so many lovely towns out that way, could do Bologna if didn't from Florence, also Padova, Ravenna, perhaps even a lake town, and of course Venice as day trip from here.

One thing I learned from my 6 week trip to Europe 3 years ago (France and Switzerland) is that you don't have to see anything specific. In some ways the towns are very similar and other ways different, but at some point it doesn't really matter which ones you see. You find they are all interesting and you can just enjoy your time wherever you happen to be. Also, there seems to be no predicting which town you may love or not love, no matter how much you hear it from other people, because we are all so different. The towns we visited then, some were gorgeous, some had interesting people, some were quiet and unassuming while others were busy. We had favorites, but then sometimes ones I didn't even realize at the time that I liked that much turned out to be the ones that stick in my mind forever. Nice, France was like that. Of all the towns it was the grittiest and dirtiest, but oh the lovely walks we took through so many varied parts of the city, the trolley and park, the uniqueness of the beaches, the tens of thousands of people filling the streets every night eating outside, the old town with it's crazy narrow streets, the grimy train that we took to all the other towns along the Riviera. I thought those other towns were so much better (quieter, prettier, more upscale), said "next time we should stay here". But somehow Nice is the one I dream about.