In the spring of 1541, after roughly two months of intense fighting in the conflict that came to be known as the Salt Wars, Vittoria Colonna's brother Ascanio Colonna surrendered to the pope. Despite fervent pleas from the Emperor Charles V to spare a few of the Colonnas’ feudal lands, Paul III razed the fortifications of Marino, Rocca di Papa, and Paliano to the ground. Ascanio was declared an enemy of the Papal States and went into exile in the kingdom of Naples, while Vittoria, who had taken refuge in Orvieto, returned to Rome to the familiar convent of San Silvestro in Capite. Of her response to the family's ruin, two mentions have survived. The first comes second-hand in a letter from the governor of Orvieto, Brunamonte de Rossi, to the pope's grandson, Cardinal Alessandro Farnese. ‘Great satisfaction’, de Rossi wrote, ‘is universally felt at the taking of Paliano, which I immediately made known and published everywhere … Nor did I fail to report the news to the Signora Marchesa, who replied: “Possessions come and go, so long as people are safe”’. The second we find in a letter Colonna wrote to her friend Ercole II d’Este, duke of Ferrara. ‘Your excellence should know’, she began, ‘that I am most consoled in my distress, and I thank God that with the loss of worldly goods, fortune has given me the occasion to acquire goods of the spirit’.

It was precisely in the aftermath of these worldly losses, and their reinforcement of her already fierce commitment to the ‘goods of the spirit’ (beni del animo), that Colonna made the decision to move to Viterbo, where a community of reformers was gathering around the newly appointed papal legate, or governor, Reginald Pole.