Altered gene expression that results in unrestricted growth and loss of differentiation is a hallmark of neoplastic cells. The goal of the present study was to determine early changes in gene expression profiles during colorectal carcinogenesis with emphasis on those genes whose expression is upregulated in adenoma tissue compared to adjacent normal colon. Using the suppression subtractive hybridization (SSH) approach on enriched colonic crypts we identified 14 candidate genes showing increased expression levels in the original adenoma sample. Subsequent dot blot, Northern blot, standard and real-time RT-PCR analysis confirmed increased transcript levels of ten genes in various subsets of colorectal adenoma and cancer samples. SERPINB5 and a yet uncharacterized HERV-H sequence showed the highest expression in adenoma and tumor samples without significant expression in the corresponding normal tissue. These genes might represent promising new candidates for colorectal cancer early detection.