The article reconstructs the complex urban stratifications of the Roman block of Trinità dei Pellegrini from antiquity to the modern era, with particular attention to the architectural language of the interventions carried out in the second half of the twentieth century by Marcello Piacentini and by Emanuele and Gianfranco Caniggia. Through extensive research conducted in the Roman archives, the study retraces the political and economic circumstances that led to the demolition and subsequent reconstruction of the historic urban fabric. Special attention is devoted to the history of the building associated with the room in which Goffredo Mameli died in 1849, having been wounded at the Battle of the Vascello during the defense of the Roman Republic. The history of the block, however, is far older: originally built on an imperial-era insula, it developed without interruption from the Middle Ages to the Renaissance, becoming further consolidated in the Baroque period with the construction of the Ospizio dei Convalescenti e Pellegrini, erected next to the church of Trinità dei Pellegrini. Transferred to the Kingdom of Italy in 1870, the complex entered a phase of progressive neglect. Under the Fascist regime it was sold to the SCI company owned by Romolo Vaselli, who obtained permission to demolish and rebuild most of the block, with the sole exception of the church and the first floor of the Refettorio Piccolo. In the postwar period, Marcello Piacentini designed a new plan for the block; however, only two of his buildings were constructed, while a third was completed by Angelo Di Castro. The land was subsequently purchased by the Angeletti family, who commissioned Emanuele and Gianfranco Caniggia to complete the project. After numerous design revisions, they succeeded in obtaining municipal approval and completing the work. Today, the Trinità dei Pellegrini block stands as a unicum in the heart of Rome, a fragment of the city in which heterogeneous architectural and linguistic experiments have succeeded one another without interruption.