The major biomarker for rectal cancer is the pathologic development of the tumor. In our study, we identified Dikkopf-1 (DKK1) as a novel biomarker and a therapeutic target for rectal cancer. To emphasize the biological and clinicopathologic significance, we performed tumor tissue and serum analysis of 150 rectal cancer samples with enzyme-linked immunosorbent assay. Serum DKK-1 levels are found significantly higher in controls, in poor differentiation, and depth of invasion (in pT3 and pT4), present lymph node metastasis, and TNM stage (in pT3 and pT4) according to good differentiation, depth of invasion (in pT1 and pT2), absent lymph node metastasis, and TNM stage (in pT1 and pT2; P < 0.001 and P < 0.0001, respectively). Tissue DKK-1 levels are found in patients with rectal cancer than in control tissues (P G 0.0001). Dikkopf-1 correlated significantly with depth of invasion (P = 0.009), lymph node metastasis (P = 0.028), venous involvement (P = 0.019), and advanced pTNM stage (P = 0.001). There was no correlation between DKK-1 and age or sex (P > 0.05). This marker is also a potential candidate for development of rectal cancer cells and cancer progression.