The aim of the study was to demonstrate the value of the double immunostaining for endothelial and perivascular cell to discriminate mature from immature tumor-associated blood vessels in mammary carcinoma. We used the specific endothelial marker CD105 to highlight the activated endothelial cells and antibodies against smooth muscle cell actin (SMA) for perivascular cells, applying Envision Doublestain system (HRP/DAB-APAAP/Fast Red). We found an inverse correlation between the immunoexpression of CD105 and SMA in normal vessels and a strong positive signal for CD105 in the intratumor single endothelial cells and immature vessels. Only few blood vessels were positive for both CD105 and SMA within the tumor area. The signal for the endothelial marker was weak and inconstant, and significantly diminished when the SMA immunoexpression was increased for the same vessel. The differentiation between vessels with and without perivascular cells coverage using double immunostaining for CD105/SMA may be an important step in the selection of the mammary tumors, which could have a high grade of responsiveness to antiangiogenic therapy with monoclonal antibodies against CD105 antigen.