Special birational transformations Φ : P r Z defined by quadric hypersurfaces are studied by means of the variety of lines Lz ⊂ P r−1 passing through a general point z ∈ Z. Classification results are obtained when Z is either a Grassmannian of lines, or the 10-dimensional spinor variety, or the E 6variety. In the particular case of quadro-quadric transformations, we extend the well-known classification of Ein and Shepherd-Barron coming from Zak's classification of Severi varieties to a wider class of prime Fano manifolds Z.Combining both results, we get a classification of special birational transformations Φ : P r Z defined by quadric hypersurfaces onto (a linear setion of) a rational homogeneous variety different from a projective space and a quadric hypersurface.