Inflammatory acute phase proteins have been reported to play a crucial role in cancer progression. Various hematologic and inflammatory markers and scores, such as the lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammation score (SIS), prognostic nutritional index (PNI), Glasgow prognostic score, and, more recently, the Naples prognostic score, have been reported as significant prognostic markers. The aim of this prospective study was to evaluate the prognostic significance of the C reactive protein-to-albumin ratio (CAR) in patients with colon cancer. : We conducted a prospective observational study on a series of patients who underwent curative surgery for colon cancer. The C reactive protein-to-albumin ratio was determined preoperatively, and we evaluated the correlations between the CAR and various clinical and pathological parameters, as well as the correlation with Overall and Relapse-free survival. Furthermore, we compared the accuracy of the CAR with that of the Naples score. : One hundred and ten patients were included in the study. We set 0.4927 as the cut-off value for the CAR according to a receiver operating characteristic curve analysis. Based on the cut-off value, patients were divided into a low CAR group and a high CAR group. The preoperative CAR exhibited statistically significant correlation with tumor volume, T and N stage, number of positive lymph nodes, and grade of tumor differentiation. We also demonstrated a positive correlation between high CAR values and a higher Naples score ( = 0.0005), even when a subgroup analysis was performed for each group individually. : The preoperative CAR is a useful prognostic marker in patients with colon cancer. These results may help to design strategies to personalize targeted management approaches among colon cancer patients.