Tuscany, then to Milan
 

We're rookies in Tuscany and need advice as to absolute best base for day trips. or would you advise a staying in a different town each night?
we want to do one day in Florence -- should we make it a day trip from our base in Tuscany or stay there our last night in the region?
Finally, when we return to Milan for our next day flight, should we take the train fromm Siena or Florence? Thanks in advance.

Without checking trenitalia.com (you should, though) I believe that train connections between Florence and Milan are better than the offerings between Siena and Milan.

Now, for your other questions: they are almost too hard to answer. Tuscany is a very large area, and there is no single "absolute best base" to stay in and see a different town each day.

My first question to you would be, "which towns do you want to see?" Based on your preferences, we could then focus on an area and discuss why any town would be a good or bad choice.

One of my choices would be San Gimignano, with day trips to Siena, Volterra, San Miniato, and maybe more. Although for 4 days, that ought to be pretty good.

Or Lucca, and visits to Pisa, and then to the many choices north of there.

Or Pienza or San Quirico d'Orcia, with visits to Montalcino, Montepulciano, San Antimo, and Siena.

Or Cortona, with visits to Poppi, Arezzo, Sansepolcro, and more.

Or Greve, with visits to Castellina, Panzano, Radda, etc.

I could keep going, but you get the idea. Just what do YOU want to see in Tuscany?

Divide Tuscany up into no more than two areas, then use them as a base for day trips etc. I would suggest the Val di Pesa area, we have stayed at Castello di Montegufoni www.montegufoni.it several times and loved it, and then perhaps the Val di Chiana area e.g. Cortona or Montepulciano.
Using those areas as our main bases we have been able to explore many towns in Tuscany (3 vacations) including all the places mentioned by the prievious poster.
Stay the last night in Florence and take the train to Milan from there.

Well my personal thinking is I would not depend on the trains in Italy the day I was flying home. I have had experiences with trains in Italy being so late..and sometimes the train employees go on strike although the strike does have to be announced in advance. If I was flying home from Italy (assume you are departing from Malpensa airport back to the US?) I would be in Milan late afternoon the day before and have a hotel room reserved in Milan. And than take the Malpensa shuttle bus from the Central Train station the next morning to Malpensa. Or if the flight was real early in the morning I would get a hotel room at a hotel at Malpensa airport.

From your comment "Finally, when we return to Milan for our next day flight"..it does sound like you are planning to be in Milan the day before your flight departs. That is good IMO. I would take the train from Florence to Milan.

And do have a wonderful and beautiful time in Italy bellemarie!!

You know, you might want to think about staying in Fiesole. It is a very short bus ride into Florence, and within the Chianti region. You would be out of the major centre, yet highly accessible to Florence, and the local train system from Florence to most of the towns listed in the emails below.
AND you can take the train from Florence to Milano direct (Eurostar). The bus into town from Fiesole is the number 7, and the trip is about 20 minutes long. As it is a city bus that takes you, it runs often, frequently, and is fairly inexpensive.

Any rail connection Siena to Milan will involve a change of train in Florence.

Many prefer to travel between Florence and Siena by bus; one reason is the bus station in Siena is somewhat more centrally-located than the train station which requires a short city bus or taxi ride into the center. The bus station in Florence is loacted close to the Santa Maria Novella RR station which is where you would leave from for your rail trip to Milan.

thanks, all.
yes, our flight from Malpensa is at noon, so that will work.
sounds like a compromise -- we'll stay in two places for the four nights and do our day trips.