MOTIVATION: The precise identification of functionally and structurally important residues of a protein is still an open problem, and state-of-the-art classifiers predict only one or at most two different categories. RESULT: We have implemented the classifier CLIPS-4D, which predicts in a mutually exclusively manner a role in catalysis, ligand-binding or protein stability for each residue-position of a protein. Each prediction is assigned a P-value, which enables the statistical assessment and the selection of predictions with similar quality. CLIPS-4D requires as input a multiple sequence alignment and a 3D structure of one protein in PDB format. A comparison with existing methods confirmed state-of-the-art prediction quality, even though CLIPS-4D classifies more specifically than other methods. CLIPS-4D was implemented as a multiclass support vector machine, which exploits seven sequence-based and two structure-based features, each of which was shown to contribute to classification quality. The classification of ligand-binding sites profited most from the 3D features, which were the assessment of the solvent accessible surface area and the identification of surface pockets. In contrast, five additionally tested 3D features did not increase the classification performance achieved with evolutionary signals deduced from the multiple sequence alignment.