Pozzuoli began as the Greek colony of Dicaearchia (Greek: Δικαιαρχία). The Roman colony was established in 194 BC, and took the name Puteoli which it has his roots from 'puteus', meaning well (also used by sibyls to predict the future) and 'osco fistulus' (cave). An alternative etymology of Puteoli from the Latin puteo (to stink), referring to the sulfuric smell in the area, most notably from Solfatara. This is because Pozzuoli lies in the center of the Campi Flegrei, a volcanic caldera.

Puteoli was the great emporium for the Alexandrian grain ships, and other ships from all over the Roman world. It also was the main hub for goods exported from Campania, including blown glass, mosaics, wrought iron, and marble. The Roman naval base at nearby Misenum housed the largest naval fleet in the ancient world. It was also the site of the Roman Dictator Sulla's country villa and the place where he died in 78 BC.

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