I am going to visit Varenna in the Lake Como region next June. We want to take couple of days and go to Switzerland. Is that possible by train? Lucerne would be nice if it isn't too far.
The faster train connections go back south to Milano or Como town before heading north toward Luzern. But the line heading north from Varenna along the east side of the lake will take you to the Swiss border at Tirano, where you can catch part of the scenic Bernina Express route. For Milan-Varenna-Tirano train schedules, see www.trenord.it, instead of our favorite DB schedules. You can see this rail line on the color maps in RS Italy or Switzerland books (or even on Google maps if you get in close).
There is a very fast train run from Milan to Lucerne. Some of these runs require a train change at Arth-Goldau. This train does stop at Como S. Giovanni which is at the south end of the lake. From Varenna-Esino, you would be best to invest the hour or so to return to Milan to catch this train. One alternative, as Laura explains, is to take the train to Tirano to take the Bernina Express. You could stay overnight at St. Moritz or Pontresina and return the next day. It's hard to do same day. Lucerne is unlikely on this run. But the Bernina Express is probably the best of the Swiss scenic trains.
We did the William Tell Express out of Lucerne and ended in Lugano. Then we did the Bernina Express when we left Lugano. The Bernina Express started with a bus in Lugano. We were treated to a long bus ride around Lake Maggiorre. We then boarded two different trains and ended in Zurich, in the evening. Both the William Tell and the Bernina Express' were outstanding.