Since 1503 Seville was the headquarters of the Casa de Contratacion, and its port on the Guadalquivir River became the main commercial nexus with the Americas. Besides other goods that are very well studied by economic historians, Seville shipped to the New World artwork such as sculptures, sumptuary objects and, above all, serialized paintings. Simultaneously, Seville received artistic and exotic goods from the Indies. This chapter analyzes the role of Portobelo and the Isthmus of Panama as a point of commerce and distribution of works of art to the rest of the Americas. It shows the importance of paintings’ retail trade in the fairs of the city and the way prices of those paintings were negotiated, normally by considering their size and the motifs represented rather than their intrinsic artistic quality. The outcome is an conception that makes it possible to contrapose this market of anonymous suppliers and consumers to the better-known market based on commissions from members of the elite or ecclesiastic institutions.