He apprenticed with his family, including his elder brother, Pellegro Piola, as well as with Domenico Fiasella. Other members of the Piola family, who were artists included Domenico’s brother, Giovanni Andrea and his three sons Paolo Gerolamo, Anton Maria, and Giovanni Battista; his two sons-in-law, Gregorio de’ Ferrari (his most distinguished pupil and married to his daughter Margherita Piola) and Domenico Parodi; and his brother-in-law Stefano Camogli. The large family studio, called Casa Piola excelled in both quadratura fresco decoration and canvases. Generations of artists, down to the 20th century, descended from the line of Piola-De Ferrari, including Giovanni Maria De Simoni, who died in 1913 in the original residence of Domenico’s family. Domenico was also a well-known printmaker and draughtsman. Domenico participated in many large fresco decorations in Genoa, including the ceiling in the Palazzo Rosso and the Basilica della SS. Annunziata. He also participated in the canvas decoration of the Oratory of San Giacomo della Marina.