AbstractWe continue the investigation of the isomorphism problem for multiplier algebras of reproducing kernel Hilbert spaces with the complete Nevanlinna-Pick property. In contrast to previous work in this area, we do not study these spaces by identifying them with the restrictions of a universal space, namely theDrury-Arveson space. Instead, we work directly with theHilbert spaces and their reproducing kernels. In particular, we show that two multiplier algebras of Nevanlinna-Pick spaces on the same set are equal if and only if the Hilbert spaces are equal. Most of the article is devoted to the study of a special class of complete Nevanlinna-Pick spaces on homogeneous varieties. We provide a complete answer to the question of when two multiplier algebras of spaces of this type are algebraically or isometrically isomorphic.This generalizes results of Davidson, Ramsey,Shalit, and the author.