Phaleria macrocarpa (Scheff.) Boerl. (Thymelaeaceae), an Indonesian native plant, has been used to treat various diseases in Indonesia. DLBS1425, a standardized extract of flesh fruit of Phaleria macrocarpa, is hypothesized to have anti-cancer activities. Anti-proliferative and induction of apoptosis conferred by DLBS1425 on breast cancer cells, MDA-MB-231 and MCF-7 cells were investigated. DLBS1425 showed an inhibition of proliferation in both cell lines. Induction of apoptosis was shown by DNA fragmentation, activation of caspase 9, and regulation of Bax and Bcl-2 at the mRNA level. DLBS1425 downregulated COX-2, cPLA2, and VEGF-C mRNA expressions. DLBS1425 also down-regulated c-fos and HER-2/neu mRNA expression in TPA- or fatty acid-induced MDA-MB-231 cells. These findings demonstrate that DLBS1425 has anti-proliferative, anti-inflammatory, and anti-angiogenic properties, which make it pharmacologically ideal for the prevention and/or treatment of breast cancer.