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Abstract: The Santacroce family assembled an important art collection during the seventeenth century. While the prestigious collection of antiquities is better known, their painting collection was also remarkable. Paintings from Bolognese masters such as Giovan Battista Ruggieri, Mastelletta, Guido Reni, Francesco Albani and Guercino were exhibited in the family’s Rome residence, next to the church of San Carlo ai Catinari. In addition the inventories include other sixteenth and seventeenth century masters such as Simon Vouet, Salvator Rosa and Orizzonte. Mattei di Paganica’s collection contributed to enrich further the selection of paintings in the Santacroce’s possession thanks to the union between Valerio V Santacroce and Faustina Mattei, who brought the paintings she had inherited from her father, duke Giuseppe to the marriage. The masterpieces of the Santacroce collection are The Magdalene and The Assumption by Guido Reni, The Four Seasons by Francesco Albani, Saint Jerome Sealing a Letter by Guercino. The inventories also indicate a good collection of drawings. With the extinction ofthe family, the entire collection was dispersed during the second half of the nineteenth century.