The Wnt antagonist Dickkopf-3 (Dkk-3) has been implicated in several stages of tumour development in a wide; range of human cancers, including colorectal cancer (CRC). However, the usefulness of serum Dkk-3 levels as a; diagnostic biomarker for CRC has yet to be determined. In this study we used an ELISA immunoassay to examine; serum Dkk-3 protein levels in a retrospective cohort of CRC patients (n = 89) and age, gender matched controls (n; = 46). The median concentration of Dkk-3 was significantly (p = 0.0003) lower in CRC patient serum samples (29.3; ng/ml, range 10.4 – 67.8 ng/ml) when compared to control serum samples (36.8 ng/ml, range 20.7 – 67.4 ng/ml).; Receiver operating characteristic analysis demonstrated at 90% specificity, serum Dkk-3 levels distinguished CRC; patients with 36% sensitivity (AUC = 0.69, 95% CI 0.60 – 0.78).