Gene regulation is the process through which an organism effects spatial and temporal differences in gene expression levels. Knowledge of cis-regulatory elements as key players in gene regulation is indispensable for the understanding of the latter and of the development of organisms. Here we present the tool jPREdictor for the fast and versatile prediction of cis-regulatory elements on a genome-wide scale. The prediction is based on clusters of individual motifs and any combination of these into multi-motifs with selectable minimal and maximal distances. Individual motifs can be of heterogenous classes, such as simple sequence motifs or position-specific scoring matrices. Cluster scores are weighted occurrences of multi-motifs, where the weights are derived from positive and negative training sets. We illustrate the flexibility of the jPREdictor with a new prediction of Polycomb/Trithorax Response Elements in Drosophila melanogaster. jPREdictor is available as a graphical user interface for online use and for download at http://bibiserv.techfak.uni-bielefeld.de/jpredictor.