We developed a new cis-regulatory module (CRM) prediction algorithm, called PhylCRM. PhylCRM combines data for individual motif occurances scored on an alignment using previously described MONKEY scoring sheme (Moses et al., Genome Biology 5, R98, 2004) into a single CRM prediction. PhylCRM can scan very long genomic sequences for candidate CRMs by quantifying both motif clustering and conservation across arbitrarily many genomes using an evolutionary model consistent with the phylogeny of the genomes.