Is it better to fly into Rome or Milan?

Fly into whichever puts you closest to your first stop, and fly home from a different one. Rome Fiumicino is the natural door to Rome, the south and Tuscany; Milan Malpensa is better for the lakes, the Dolomites, Venice and the northwest. Both have fast trains into the country's rail spine. Milan often has cheaper transatlantic fares and a shorter flight from the US East Coast. The bigger decision isn't which one — it's booking an open-jaw ticket so you don't spend a day travelling back to where you started. Airlines price these almost identically to round trips.