Lo Spagna is known for a number of major works completed in the region, including the Birth of the Virgin from Spineta in Todi,[1] the Adoration of the Magi of Ferentillo[2] and the Nativity of St Anthony in Perugia.
[3] Lo Spagna married Santina Martorelli from one of Spoleto's leading families and here he was nominated Capitano delle Arti dei Pittori e degli Orefici in 1517.
The apse of the church of San Giovanni Battista in the small village of Eggi contains a fresco completed by a hand from Lo Spagna’s studio working from a drawing by the artist.
For the church of San Martino, Lo Spagna completed the large altar-piece of Coronation of the Virgin, (1522), which today hangs in the Museo Civico of Trevi.
Lo Spagna painted a fresco cycle for the parish church of San Michele Arcangelo in Gavelli, a hamlet in the township of Sant'Anatolia di Narco near Perugia.