We studied the effects, either combined or alone, of lectin from Korean mistletoe (Viscum album var. coloratum agglutinin, VCA) and doxorubicin (DOX) in MCF-7 (estrogen receptor-positive) and MDA-MB231 (estrogen receptor-negative) human breast cancer cells. When VCA and DOX were combined, a strong synergistic effect was shown in cell growth inhibition, compared to VCA or DOX treatment alone. In quantitative apoptosis studies analyzed by flow cytometry, a combination of two agents showed an increase in apoptosis in both cells, compared to agents alone. Also, pro-apoptotic proteins including Bax, Bik, and Puma were increased in both cells, and the survival factor Bcl-2 was inhibited in MCF-7 cells when drugs were combined. Furthermore, VCA combined with DOX mediated S phase arrest, accompanied with a decrease of cell number at G0/G1 phase. This suggests that VCA and DOX combination may possibly lead to a novel strategy for the treatment of breast cancer.