Getting around Milan

To the Duomo and Galleria (they are next to each other) take the tramway no. 14 from Viale Certosa near the hotel.
To Santa Maria delle Grazie (last supper) take the no. 19 tramway from viale Espinasse (et off at Piazza Conciliazione and walk).
35-40 min door to door in both cases.

I would do it the day before flying home if you depart from Milan, since you probably need to spend the last night in Milan regardless, but it's up to you if you want to do it at the beginning or the end of your trip.

One more thing. If you use Malpensa (MXP) airport (the largest of the 3 Milan area airports), it is very far from the city and the taxi from/to your hotel is probably around €90. A better option is to take the Malpensa Express train to the Cadorna station and a taxi or tram from there. But it depends on how many people are traveling together and therefore sharing the high taxi cost. The train is €12 pp each way from/to MXP.

One thing I like to do when I arrive (or even before departing) to MXP is to spend some time on Lake Maggiore (Stresa or Arona), which is closer to MXP than Milan itself. That might be a very viable alternative to lake Como, which is a bit of a detour for your intended itinerary. Actually I have always preferred lake Maggiore to Lake Como, but for some reason Rick Steves loves Varenna and all of his followers can't even fathom of deviating from where he goes (like Castelrotto for the Dolomites. Really? Castelrotto over the Val Gardena?)

Roberto

Thanks for such detail. I have done a lot with Rick's tools and advice when traveling with family, but the reason for this solo trip is to do things a bit different. I am open to any new opportunity that may present itself and like many others thought Lake Como was THE thing to do in that part of Italy. I'll look into the lake you recommended as an easier alternative. As for the three places I want to see, I can try to do it early or late in my journey. I thought of the Doubletree because I have lots of Hilton points I can use. I don't mind a long tram ride into the center of the city or the cost and would use it to get acquainted with the city. I do not have recommendations for a more simple hotel or B&B there. I do have a room on the night before I leave for home at the Hilton Garden Inn about 4 miles from the airport and they have a free shuttle. Strange as it may seem, I just learned that May 1 is a national holiday and my original plan to go to Venice on 4/30 might be affected by the crowds and lack of accommodations. The info I received said Milan would be less affected, so I thought I might stay several days there and then go to Venice. Is it worth staying three days in Milan? If I did then I could arrange to arrive in Milan the day before I leave with nothing of consequence to do except maybe the lake. Thanks again.

I have never liked Milan too much and to me anything more than 2 nights (1 full day) would be a waste. It takes 20 minutes to see the last supper (reservations mandatory), 20 min to see the Galleria and a little longer to see the Duomo (next to the Galleria). La Scala Opera theater is also on the other end of the Galleria. The Castello Sforzesco has a few nice museums as well. Besides that, if you like paintings the Pinacoteca di Brera is worth a visit. All of the above can be done in a full day.
Personally when I land at Malpensa I like the idea of spending 3 nights in Stresa to get acquainted with the time zone. There is no better place to do so than on the lake shore of one of the most beautiful lakes in Europe. Don't forget to take a boat trip to the Borromee islands if you do.

Obviously Roberto has a much better grasp on the all of this than I do, but I'd like to put in a vote for Milan – Depending on your interests. I spent three happily occupied days there on my first visit. There are some really beautiful very early churches, dating back to shortly after the edict of Milan, if that interests you. Also I thought the collections of both the Brera and Ambrosiana (sp?) galleries were really lovely, and no where near as crowded as major museums in other cities. Because things are spread out throughout the city, it does take a little time to get around; I would have appreciated a fourth day there.

When you visit the Duomo, make sure to make time to go up to the roof. I also enjoyed the excavations under the Duomo.

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I love Milano and go there often, usually flying in or out from the US. Three nights would give you time to recover from the flight, see the essential sights of Milano, and perhaps take a daytrip to someplace nearby (Bergamo is only an hour away and a very different vibe). Favorite hotels in Milano are the Hotel Garda and Hotel Berna, both very near Milano Centrale.

Or, stay elsewhere (like Stresa) and plan a full day in Milano, you can visit three or four sights in a long day.

Be aware that for Leonardo's Last Supper you need an hour, including arrival time ahead of your reservation and the 20 minutes you will be permitted to see the painting. There is a photo display in the waiting area that can fill your pre-visit time.

Roberto - 51% of Americans choose Lake Como on the chance of running into George Clooney.

Stan, then Vernazza is not the place to go. Clooney's house is in Laglio.