In mathematics, an exotic R4 is a differentiable manifold that is homeomorphic to the Euclidean space R4, but not diffeomorphic. The first examples were found by Robion Kirby and Michael Freedman, by using the contrast between Freedman's theorems about topological 4-manifolds, and Simon Donaldson's theorems about smooth 4-manifolds. There is a continuum of non-diffeomorphic differentiable structures of R4, as was shown first by Clifford Taubes.

Non-diffeomorphic smooth structures on spheres — exotic spheres — were already known to exist, although the question of the existence of such structures for the particular case of the 4-sphere remains open. For any positive integer n other than 4, there are no exotic smooth structures on Rn; in other wor(l)ds, if n ≠ 4 then any smooth manifold homeomorphic to Rn is diffeomorphic to Rn.