From Milan :

take the autostrada del Sole A1 Milan -Orvieto (444 km) and then the state road 71 first, then 74 until Pitigliano (54 km).

From Florence :

take the superstrada Firenze-Siena. Then take the Via Cassia towards Rome until San Lorenzo Nuovo (VT). Afterwards, take the state road 74 towards Grotte di Castro (VT) and after 30 km there is Pitigliano.

From Rome:

take the autostrada Rome – Civitavecchia (A12), then the via Aurelia until Montalto di Castro, Canino, Valentano and Pitigliano.

Or:

take the Via Cassia until Viterbo, then, driving round the shore of the Bolsena Lake , go towards Valentano and then, through the state roads 71 and 74 continue for 20 km until Pitigliano.

From Livorno / Grosseto

Take the state road 1 Aurelia until Albinia, continue through the state road 74 towards Manciano and (at 18 Km from it) Pitigliano.