Background: The increasing complexity in colon cancer treatment has generated a need to discover novel predictive biomarkers. No biomarker exists that can accurately stratify patients for optimal therapy nor effectively monitor for a favorable response.YKL-40, a serum secreted glycoprotein of the chitinase gene family, has been detected in patients with cancer and has correlated with metastasis and a poor prognosis. To date, the expression profile of YKL-40 has not been described in colorectal cancer. We therefore investigated whether expression of YKL-40 is tumor specific in primary colorectal cancer and is conserved in metastatic disease in hopes of developing a reproducibly measurable biomarker to correlate with cancer phenotype and to help guide therapy. Materials and Methods: Data from tumor registry and medical records identified 175 patients with Stage IV disease. Patients were selected based on available tissue from distant metastases. YKL-40 expression was analyzed by immunohistochemistry performed on the original tumor, lymph node and distant metastasis. The tissue staining was scored by the intensity and percentage of positively stained cells. Results: Ten patients were identified with obtainable tissue specimens to measure YKL-40 expression. YKL-40 expression was equally expressed by intensity and percentage scores in the primary tumor, metastatic lymph node and distant metastasis within each patient. Expression profile was conserved irrespective of the treatment with chemotherapy and/or radiation. Interestingly, an increased expression of YKL-40 occurred in inflammatory cells within the stroma recapitulating the profile of expression in the primary and metastatic tumors.Conclusion: Our preliminary results demonstrate the conservation in expression of YKL-40 with advanced and metastatic colorectal cancer. YKL-40 is ubiquitously expressed in Stage IV disease with a pattern that is conserved in the primary and metastatic tissues irrespective of treatment. The preliminary data also suggest that YKL-40 may serve as a good biomarker to guide treatment for Stage II and III colon cancer. The presence of expression within infiltrative inflammatory cells supports a role of YKL-40 in the inflammatory process but raises question to the origin of serum-secreted protein. Further data analysis is underway to confirm our results and to explore the validity of YKL-40 as a predictive biomarker for colorectal cancer.