It is known that cancer is not a single transformational event. It is rather a multistage process involving complex interactions with the surrounding cellular microenvironment. Mast cells accumulate at sites of tumor growth in response to numerous chemoattractants. Our aim was to investigate the relationship between mast cell density (MCD) and myometrial invasion in endometrial carcinomas. Immunohistochemistry was performed on 35 unselected consecutive hysterectomy specimens from patients with endometrial adenocarcinoma. C-kit-positive mast cell assessment was performed in the myometrium adjacent to tumor tissue. A mean number of <or=15 mast cells per high power field (HPF) were regarded as low mast cell density (L-MCD), and a count of >or=16 mast cells was regarded as high mast cell density (H-MCD). A significant correlation (p=0.018, Pearson Chi-Square test) between H-MCD and the presence of myometrial invasion was demonstrated in endometrial carcinomas. H-MCD was found in 54% of all cases, and 94% of H-MCD cases had myometrial invasion, suggesting a role of mast cells or an interaction with tumor. Therapeutic modalities orientated to these cells or their microenvironment as a new target for adjuvant treatment might determine the prognosis in endometrial carcinomas.