PURPOSE: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most frequently used tumor markers in the clinical setting of colorectal cancer (CRC). This study was designed to investigate the correlation between preoperative serum levels of CA 19-9 (pre-CA 19-9) and the clinicopathologic factors of patients with CRC. METHODS: A study was performed on 333 patients with histologically diagnosed colorectal adenocarcinoma between December 2008 and November 2011, based on prospective collected data. The clinical data such as age, sex, location of tumor, size of tumor, differentiation, depth of tumor (T), lymph node metastasis (N), distant metastasis (M), lymphatic invasion, venous invasion, perineural invasion, stage, and preoperative serum levels of CEA (pre-CEA) and pre-CA 19-9 were obtained. These patients were classified into two groups according to pre-CA 19-9 (CA 19-9 high: >39 U/mL, n = 61 [18.3%]; CA 19-9 normal: <39 U/mL, n = 272 [81.7%]). RESULTS: Sixty-one patients among 333 patients (18.3%) with CRC showed a high pre-CA 19-9. The elevation of pre-CA 19-9 was significantly associated with size of tumor (4.8 +/- 0.1 cm vs. 6.1 +/- 0.3 cm, P < 0.001), right colon cancer (P < 0.001), depth of tumor (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001), perineural invasion (P = 0.008), peritoneal seeding (P < 0.001), and stage (P < 0.001). On multivariate analysis, high pre-CA 19-9 was shown to be independently associated with high pre-CEA, lymph node metastasis, right colon cancer, large tumor size, and peritoneal seeding. There were twelve patients confirmed for peritoneal seeding among 333 patients (3.6%). CONCLUSION: High pre-CA 19-9 in advanced colorectal cancer might provide important information to predict the possibility of peritoneal seeding.