ESTs and full-length cDNAs represent an invaluable source of evidence for inferring reliable gene structures and discovering potential alternative splicing events. In newly sequenced genomes, these tasks may not be practicable owing to the lack of appropriate training sets. However, when expression data are available, they can be used to build EST clusters related to specific genomic transcribed loci. Common strategies recently employed to this end are based on sequence similarity between transcripts and can lead, in specific conditions, to inconsistent and erroneous clustering. In order to improve the cluster building and facilitate all downstream annotation analyses, we developed a simple genome-based methodology to generate gene-oriented clusters of ESTs when a genomic sequence and a pool of related expressed sequences are provided. Our procedure has been implemented in the software EasyCluster and takes into account the spliced nature of ESTs after an ad hoc genomic mapping.