AIM: To determine whether the mast cell (MCs) and tumor-associated macrophage (TAMs) counts have any correlation with clinical outcome in colorectal cancer, and to investigate whether MCs undergo phenotypic changes in colorectal cancer.METHODS: The MC and TAM counts were determined immunohistochemically in 60 patients with colorectal cancer and the depth of invasion, lymph node metastasis rate, distant metastasis rates, and survival rates were compared between patients with low (less than the mean number of positive cells) and high (more than the mean number of positive cells) cell counts.RESULTS: Both patients with a low MC count and patients with a low TAM count had significantly deeper depth of invasion than those with a high MC count and those with a high TAM count (P＜0.01 and P＜0.01 respectively).Patients with a high MC count and patients with a high TAM count were significantly higher showing significantly lower rates of lymph node metastasis, distant metastasis than those with a low MC count and those with a low TAM count. There were significant positive correlation between MC counts and TAM counts (r = 0.852, P＜0.01).In both cancerous tissue and normal colorectal tissue,the predominant MC phenotype was MCTC. The 5-year survival rate estimated was significantly lower in both patients with a low MC count and patients with a low TAM count than in those with a high MC count and those with a high TAM count (P＜0.05 and P＜0.01 respectively).CONCLUSION: There appears to be a direct relationship between the number of MCs and clinical outcome in patients with colorectal cancer, even though MCs exhibited no significant phenotypic changes. TAM count is of value to predict the clinical outcome or prognosis. It is more beneficial for estimating biological character of colorectal carcinoma to combine MC and TAM counts.