First-time visitors to Milan might be interested in joining a city sightseeing tour. These tours are not cheap (€ 55 per person in 2009) but cover all major highlights (including a guaranteed visit of the Last Supper), and can be a good introduction to Milan and its beauties. They are led by multilingual tour guides. The two operators offering these tours are Autostradale and Zani Viaggi

Zani Viaggi also offers a hop-on, hop-off tour bus service (audioguides are provided).

If you are looking to do a tour only in English there are tours which you can book on, Select Italy, or tickitaly.

More adventurous (and/or budget-minded) visitors might like to ride on the #1 tram from Via Settembrini (two short blocks from the E side of Milan's central train station where shuttle buses from airports arrive) to the Cadorna train station (where the train from Malpensa airport arrives). This tram line is still operated with vintage vehicles built in 1928 (a few identical trams have been shipped to the USand are in use on the 'F' streetcar line in San Francisco), and the route takes in several major highlights, notably Via Manzoni (skirting Via Montenapoleone and the fashion area), La Scala opera house, and the Castello Sforzesco.  Trams do not run in front of the Duomo itself (tracks were removed from the Duomo square several years ago), but you can walk from La Scala to the Duomo, through the Galleria Vittorio Emanuele, in less than 5 minutes. A standard € 1.50 ticket, bought from a newsstand, is valid for unlimited rides on trams/buses, as well as one subway ride, for 90 minutes from stamping it for the first time (but swipe it in the little red machine any time you board a tram) -- more information on public transport in the dedicated 'Inside Milan' page.