To clarify the pathophysiological role of tumor-associated macrophages (TAMs), we performed clinicopathological analysis of CD68+ cells in 70 cases of human endometrial cancer. Using immunohistochemistry for CD68, we classified CD68+ cells into four groups: (a) those infiltrated into cancer cell nests or in close contact with cancer cells (nest TAM); (b) those in necrosis in the tumor center (hot-spot TAM); (c) those infiltrated into cancer stroma (stroma TAM); and (d) those distributed along the invasive margin of a tumor (Margin TAM). The aggregation of nest TAM related to high relapse-free survival rate after surgery. On the contrary, increased hot-spot TAM was a hazard to relapse-free survival and was proportionately-associated with clinical stage, myometrial invasion and histological differentiation. The extent of stroma TAM was associated with the presence of lymph node metastasis. Our findings demonstrate that the histological location of infiltrated TAMs may be taken into account in the clinical evaluation of endometrial cancer.