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The church and convent of San Pio were built on the ruins of an ancient Roman imperial villa probably inhabited by the emperor Antonino Pio. The villa was still visible until 1838 when it was described by Senni in his book ‘Memoirs of Genazzano’.

In 1910 a mosaic floor was discovered which is now in the Museo Nazionale delle Terme in Rome.

The monastery dates back to the middle of the fifteenth and seventeenth centuries and the marble portal inscription refers to Pius II Piccolomini. The lunettes of the cloister are decorated with frescoes by Vincenzo Manenti and depict St. Francis.