Genome scans have been used in the studies of ecological speciation to find genomic regions (‘outlier loci’) showing reduced gene flow between divergent populations/species. High-throughput sequencing (‘454’) offers new opportunities in this field via transcriptome sequencing. Divergent ecotypes of the marine gastropod Littorina saxatilis represent a good example of incipient ecological speciation. We performed a 454-based genome scan between H and M ecotypes of L. saxatilis from the British Isles using cDNA of pooled individuals. Allele frequencies were calculated for 2454 single nucleotide polymorphisms (SNPs), within 572 contigs, and 7% of loci were detected as outliers. Functional annotation of the contigs containing outlier SNPs showed that they included shell matrix and muscle proteins (lithostathine, mucin, titin), proteins involved in energetic metabolism (arginine kinase, NADH dehydrogenase) and reverse transcriptases. Follow-up investigations into these proteins and unannotated outliers will be a promising route in the study of ecological speciation in L. saxatilis.