Berthold played a major role in the War of the Keys between the Empire and the Papacy in 1228–1230, leading the invasion of the march of Ancona, for which he was excommunicated.
In 1233, he left Italy for Germany, where he joined the court of Frederick's son, King Henry VII, who seems to have briefly recognized him as duke of Spoleto before he disappears from the historical record.
In September 1217, Berthold was in Rome representing his older brother Rainald in negotiations with Pope Honorius III.
In late 1218, Berthold returned to Rome, where he negotiated a settlement for his father's widow (probably not his mother), giving her control of the city and county of Nocera, but could not come to terms on the question of the duchy.
They forced the inhabitants to swear oaths of fealty to Frederick, now emperor, but on 22 November he ordered them to cease and desist.
[2] On 20 May 1226, Frederick II appointed Berthold as a vicar in Tuscany under the authority of his brother Rainald, who was the imperial legate there.
[2] In January 1227, Honorius III complained to Frederick II that Berthold was committing depredations in papal territory.
Upon being told that it concerned his dispute with the cathedral of Rieti, he refused to accept it, telling the envoy, "Go and stick the letter up a donkey's arse".
In late November, Pope Gregory IX excommunicated Frederick, Rainald and Berthold, the latter expressly for illegally occupying the castle of San Quirico.
In April 1233, Frederick sent Rainald in the custody of the justiciar Henry of Morra to Antrodoco to induce Berthold's surrender.
[2] Following his surrender of Antrodoco, Berthold went to Germany, then ruled by Frederick's young son, Henry VII, was pursuing policies at odds with his father's.