Our data show that (i) the TUSC3 gene was silenced by DNA methylation of its promoter in tumor tissue of a large subset of CRC patients, (ii) loss of TUSC3 mRNA expression by DNA methylation was an early event already in adenomas and also detectable by reduced TUSC3 protein levels in resected benign adenomatous polyps, and (iii) low TUSC3 protein positivity in early stage CRC patients correlated with poor clinical outcome. The gene discussed is TUSC3; the disease is neoplasm.