Background: Spiny mice of the genus Acomys are small desert-dwelling rodents that display physiological characteristics not typically found in rodents. Recent investigations have reported a menstrual cycle and scar free-wound healing in this species; characteristics that are exceedingly rare in mammals, and of considerable interest to the scientific community. These unique physiological traits, and the potential for spiny mice to accurately model human diseases, are driving increased use of this genus in biomedical research. However, little genetic information is currently available for Acomys, limiting the application of some modern investigative techniques. This project aimed to generate a reference transcriptome assembly for the common spiny mouse (Acomys cahirinus). Results: Illumina RNA sequencing of male and female spiny mice produced 451 million, 150bp paired-end reads from 15 organ types. An extensive survey of de novo transcriptome assembly approaches of high-quality reads using Trinity, SOAPdenovo-Trans, and Velvet/Oases at multiple kmer lengths was conducted with 49 single-kmer assemblies generated from this dataset, with and without in silico normalization and probabilistic error correction. Merging transcripts from 49 individual single-kmer assemblies into a single meta-assembly of non-redundant transcripts using the EvidentialGene 'tr2aacds' pipeline produced the highest quality transcriptome assembly, comprised of 880,080 contigs, of which 189,925 transcripts were annotated using the SwissProt/Uniprot database. Conclusions: This study provides the first detailed characterization of the spiny mouse transcriptome. It validates the application of the EvidentialGene 'tr2aacds' pipeline to generate a high-quality reference transcriptome assembly in a mammalian species, and provides a valuable scientific resource for further investigation into the unique physiological characteristics inherent in the genus Acomys.