Fuzzee allows the identification of functionally similar molecules, based upon functional and structural groups or fragments. The softening of the similarity definition of molecules allows scaffold hopping without additional effort. The algorithm can be used for the identification of topologically different molecules that share similar physico-chemical features. Compared to competing reduced graph or tree based approaches it has the advantage that it allows a weighted matching on the one hand and does not make assumptions on the topology of the molecules on the hand. Fuzzee is highly efficient, allowing more than 1.000 comparisons per second.