We revisit the question of frame equivalence in Quantum Field Theory in the presence of gravity, a situation of relevance for theories aiming to describe the early Universe dynamics and Inflation in particular. We show that in those cases, the path integral measure must be carefully defined and that the requirement of diffeomorphism invariance forces it to depend non-trivially on the fields. As a consequence, the measure will transform also non-trivially between different frames and it will induce a new finite contribution to the Quantum Effective Action that we name frame discriminant. This new contribution must be taken into account in order to assess the dynamics and physical consequences of a given theory. We apply our result to scalar-tensor theories described in the Einstein and Jordan frame, where we find that the frame discriminant can be thought as inducing a scale-invariant regularization scheme in the Jordan frame.