Flight out of MXP late afternoon - last night in Florence, Milan, or ??

If you had a few more nights I would have suggested 2 or 3 nights at Stresa, on lake Maggiore, which is near MXP. But in your case I would spend the last night in Milan. Price for the Last Supper doesn't increase as u get closer to the date, it's not like airfare. However you need advance reservations which are hard to get. However there are a few other things to do and see in Milan, which will keep you occupied the day before your flight and a few hours in the morning.
From the city to MXP you take the Malpensa Express train from the Cadorna station, near the Sforza Castle and the Duomo (35 min train journey for €12 per person). Google Malpensa Express and the website will come up. Don't go by taxi from Milan because MXP is far and the taxi is €95, a rip off, and takes longer than the train.

You could also stay in Firenze and go there in the morning of departure. In that case you would take a high speed train to Milan Centrale (1h45min journey) then a train to MXP ( also called Malpensa Express) from Milano Centrale to MXP (46 min).
To see schedules use
www.trenitalia.com
The station names you enter are:
FIRENZE SANTA MARIA NOVELLA
MALPENSA AEROPORTO
There are many trains to Milan (a couple per hour) but give yourself some cushion in case of Murphy's law events.

Grazie, Roberto! Aside from the Last Supper, what would you recommend in Milan?

The Duomo (you can go up to the roof), the Galleria right across the street, Castello Sforzesco has a museum and beautiful grounds for a last walk-around, Brera Gallery, several interesting churches; enough to do for a short stay.

I tell my experience. I live in Florence but my wife has an home in Milan so we travel fairly frequently between the two cities.

Consider that in order to leave at 4pm you should better be at MXP by 1pm. If you leave Florence at 10am you can be at MXP at 12.46pm. - You may add some safety time leaving at 9am or 8am or even 7.30am.

To be sincere, at this time the Frecciarossa service is fairly regular. Apart from the case of a strike - that would be announced in advance, anyway - a 1-hour safety margin covers most possible delays. A 2-hours margin covers really most of the unlikely events.

In real world you can leave Florence at 8am and be reasonably sure to make it to MXP by 1pm under most circumstances. But consider that a disruption of service (say, a suicide over the tracks, closing the line for two hours, with trains being rerouted to the slow line and some chaos), while highly unlikely, cannot completely be ruled out. If missing the flight would be a real problem (not only an inconvenience) to you, you could consider staying in Florence till 6pm or 7pm the day before and sleeping in Milan near the Centrale station (just notify the hotel you are arriving late). This would buy you some peace of mind as once you are in Milan, if the worst comes to the worst you are only a one-hour, 100 euro taxi ride from MXP.

Considering how early you would have to from Florence, probably this could be the most sensible thing to do. Things to do in Milan? IMHO, were Milan anywhere in the world, it would be considered a worthy tourist destination. But it is in Italy, competing with places like Florence and Venice, it becomes a second or third choice. Museums like Brera Gallery or Poldi Pezzoli are second choice to Uffizi and Vatican, but would be a first choice in most places of the world. Personally, having three early hours in Milan, I would just drop by the Cathedral square, have a look to the Cathedral and Galleria, maybe have a look to la Rinascente department store, the most elegant in Italy (opening at 9.30am), and it would already be the time to go back to your hotel to pick up luggage.

Forget about an intermediate destination. Parma is a nice city, but the inconvenience of not being a stop on the fast train lines makes it unfeasible for your problem. You have a choice between sleeping in Florence or Milan.

I enjoyed these sights- The Duomo, the Galleria, La Scala, and the Golden Quadrilateral (for me,mostly window shopping). Milan has a completely different feel than your other destinations and in my opinion is worth seeing.
The Sforza castle has Michelangelo's last sculpture- not as impressive as the David, but a coda none the less. You could easily decide to pay for Last Supper tickets through a middleman with a few days notice. If you are not burned out on art, the Brera has some worthy paintings.
I would stay at a modest hotel near Central Station, have a great meal and a good sleep, then take the train to the airport in comfort the next day. The Berna is a modest and friendly place with a big Italian breakfast spread.

Stay in the city of Milan. You can gain access to The Last Supper by taking certain city tours. Seeing it is one of my all time travel highlights and I have traveled extensively.
See the Duomo, and La Scala. It is a vibrant city with excellent dining.

I too felt somewhat lukewarm about a day in Milan. But, in the company of the Italian teacher I spent a week with this summer, I had a very enjoyable day and would go again. Here are the highlights of what we did: Duomo, La Scala, Chiesa di San Maurizio al Monastero Maggiore, Sforza Castle, Galleria Vittorio Emanuele II. We had a lovely lunch at a small wine and sandwich bar and an exquisite gelato in late afternoon, and that made a full-enough day.

The one unusual item on this list, the Chiesa di San Maurizio, was really stunning. The interior is completely covered in magnificent frescoes, all of which have been recently restored. My teacher said that she walked past it for decades when she worked in Milan, as it was run down and uninteresting. It's spectacular now, and something "off the beaten track" to check out. Here's the Wikipedia article about it. It's an easy walk from the Duomo, but far enough that you have to be looking for it. My second favourite item on this list was Castello Sforzesco. There are a number of different museums in the complex, so we enjoyed several hours just poking around.

So, in summary, there's plenty to enjoy in Milan if you want to spend a relaxing last day. My other observation is that 3 years ago, my family and I actually did miss our plane home from Geneva because we were just a bit too far away and got just a little lost. Since then, I'm a fan of getting close enough to guarantee that can't happen again. Your risk, your judgment...

In addition to what others have already said, you can take a walk along the Navigli, the old water canals of Milan, now a very nice place, full of restaurants and shops, a really nice atmosphere. You could also walk around Beers, known as the Artists Quarter, where you can find small artisan shops and galleries, walk the cobblestone streets... Milan is really unknown compared to other cities in Italy, but it has a lot to offer! And now after Expo, the city looks best than ever!

My husband and I had the same dilemma... we recently returned from our trip on a similar flight... Emirates I assume. I wasn't too keen on spending time in Milan but we had the chance to have dinner with a cousin who lives there and had just returned from a lengthy trip. In the end, we spent our last two nights there and were very glad we did! The city was exciting and vibrant, and the sights others mentioned are definitely worthy. I would second the suggestion to spend an evening along the Navigli. Also near this area, check out the restaurant Zio Pesce if you like seafood...best meal of our 18-day trip! Another budget hotel option is the Ostello Bello Grande. Actually a hostel but they have some nice private rooms at a great price. Late 11:30 checkout with under a minute walk to Centrale where you can catch the 11:55 Malpensa Express!

Spend the night in Milano and reduce the chances of missing your flight. We like Milano and always find interesting activites while we are there.

Buon viaggio,

Thanks very much! I appreciate all of the new suggestions for what to see while in Milan, the reasoned advice about how and when to get there, and the suggestion of a place to stay there.Cheers!

We only stay at the Hotel Berna on Via Napo Torriano when we are in Milano. It is an outstanding property, the staff is excellent, the cleanliness is outstanding, and they serve the best breakfast in the city. It is about 400 meters from Stazione Centrale and it is near all types of public transport.

Buon viaggio,

Echoing RB. Berna.

Thanks, Nigel and RP!

Oops - sorry about that, RB!

I think it's good advice to be in the city of your departure the night before any international flight. Looks like you have lots of great suggestions for passing the time in Milan!