The Marche region of Italy, long under the rule of the powerful della Rovere family, produced fewer notable musicians than other regions of Renaissance Italy. One little known master stands out for his contributions to sacred music, written under the watchful eye of both Guidobaldo II, Duke of Urbino, and his brother Cardinal Giulio Feltro della Rovere. Francesco Lupino, a native of Ancona, is revealed here as the first prominent maestro di cappella of this region, who built the musical establishments in Fano, then at the Santa Casa of Loreto, and finally at the SS Sacramento in Urbino. Recognized in his day as an eminent composer and liturgist, Lupino's music has remained in obscurity, despite the publication of his Primo libro di mottetti by Gardano in 1549, from which works were widely disseminated to German, French, and Eastern Europe sources. This study presents new documentation on Lupino's life and music that confirms his role in the development of Italian sacred music, including the emerging polychoral style, and his association with a well known circle of composers and theorists of his days.