Italians representing Spain were employed by the government or by private business. Tiburzio Spannocchi (Tiburcio Spanoqui) was a chief engineer. Christoforo Spinola (Xristobal Despindola), Bernardo Peloso, and Jacomo Rolando went to Florida with De Soto. Francesco Messina (Francisco de Mecina) crossed over the Isthmus of Panama with Balboa.

Marco Da Nizza (Marcos De Niza), together with Estevancio (an African) and Friar Onorato, traveled into the heart of Arizona and discovered present-day Phoenix. De Niza was best known for having explored the Seven Cities of Cibola—allegedly filled with gold. However, one of the most memorable Italians from Spain during the 17th and 18th centuries was Father Kino.