Cento partite sopra passacaglia (1637), the longest keyboard work by Girolamo Frescobaldi (1583–1643), consisting of over 100 tonic-dominant harmonic cycles, exhibits the composer's expansive conception of the art of variation. This article demonstrates that the overarching formal structure in Cento partite is delineated by interconnected variation processes involving the relative stability/instability of the parameters of genre (passacaglia, ciacona, and corrente) and key (motion away from and returning to the original key of D minor). These large-scale variation processes relate to and affect rhythmic and motivic content and variation on the local (variation-to-variation) level.