The Cancer Genome Anatomy Project (CGAP) database has thousands of Expressed Sequence Tags encompassing both known and novel genes. Bioinformatics of the CGAP database led to the prediction that Single Minded Gene (sim2) could be specific to colon tumors. The sim2 gene is located in a minimum region of the chromosome 21 often implicated in trisomia called Down's Syndrome Critical Region. To date, the sim proteins have not been shown to be involved in cancer. Intrigued by the possible association of a Down's syndrome-related gene to solid tumors, efforts were undertaken to validate the expression specificity. The sim2 isoform (sim2-short-form, sim2-s) expression was seen in carcinomas of colon, pancreas and prostate, but not in corresponding normal tissues. Stage-specific expression of the sim2-s protein was seen in normal matched paraffin sections of the colon tumors. In a matched set of tissues of Benign Prostatic Hyperplasia (BPH) and prostate carcinomas, sim2-s expression was detected in the BPH. The expression specificity of sim2-s in select solid tumors offers both diagnostic and therapeutic potential and warrants additional study.