The tumor microenvironment plays a pivotal role in cancer progression. The purpose of the present study was designed to evaluate the predictive value of peripheral absolute monocyte count, tumor-associated macrophage, microvessel density, and to clarify the correlation between them in patients with colon cancer.A series of 216 patients with colon cancer were enrolled in this study. The peripheral absolute monocyte count was obtained from preoperative routine blood test. Tumor-associated macrophage and microvessel density were assessed on tissue microarray by immunohistochemistry.The one, three, five-year overall survival rate for the low absolute monocyte count group was 98.4%, 91.1%, 87.1%, respectively; and for the high absolute monocyte count group was 94.6%, 83.7%, 77.2%, respectively (P = .046). The one, three, five-year progression-free survival rate for the low absolute monocyte count group was 94.4%, 87.1%, 85.5%, respectively; and for the high absolute monocyte count group was 90.2%, 75.0%, 73.9%, respectively (P = .024). Univariate and multivariate analysis showed that there was a strong association between peripheral monocyte count and clinical outcome. The correlation between peripheral absolute monocyte count, tumor-associated macrophage, and microvessel density were not observed.The peripheral absolute monocyte count was an independent prognostic factor for overall survival and progression-free survival in colon cancer. The high absolute monocyte count was significantly associated with poor outcome.