Best way to get to Spain from Italy?

Unless you're in Milan, the best, fastest and possibly cheapest way is to fly. And if your pass doesn't include France, it is worthless to go from Italy to Spain.

I don't think the ferry's such a red-hot deal. It'll stiff you about fifty euro a head as deck cargo and twice that for a cabin. The trip is twenty-some hours from Rome to Barcelona, maybe a bit less from Livorno.

From where in Italy. If you already have a rail pass, then that probably would be the cheapest. Remember cheapest, best, and quickest do not always go together well. Without the pass, a discount airline would been the cheapest unless you have a lot of luggage. Need a few more details before we can have a good answer for you.

I will be in northern Italy so Milan is practical to get to. I do not have a pass for France. I scheduled woofing in Italy then Spain, not realizing the distance between the two and unfortunately I have already bought my eurorail passes for Spain/Italy and France/Germany.
I will have to check a backpack which will probably weigh 50lbs. So I don't know if ferry and flying will just end up being approximately the same and I should just go with flying because it is faster. Time isn't necessarily an issue however. I am mainly striving for cheap.

Go to www.skyscanner.com to check out discount European flights. Just be sure to read the FINE PRINT as luggage size, weight, can cause a steep fine. Everything may be extra, seat assignment, snack, drink, etc. But if you book early enough, the flight can be really cheap.

You can fly very cheaply from Pisa to Barcelona on Ryan Air. You can also check Meridiana from Florence to Barcelona.