Technical Abstract: Scutellaria is a traditional herbal remedy with potential anti-cancer activity. The purpose of this study was to evaluate the anti-cancer mechanisms of thirteen Scutellaria species and analyze their leaf, stem and root extracts for levels of biologically active flavonoids commonly found in Scutellaria species: apigenin, baicalein, baicalin, chrysin, scutellarein, and wogonin. The extracts and individual flavonoids inhibited proliferation of malignant glioma and breast carcinoma cells without affecting primary or non-malignant cells. The flavonoids exhibited different mechanisms of anti-tumor activity as well as synergistic interactions. The anti-tumor mechanisms involved induction of apoptosis and cell cycle arrest at G1/G2. Of the extracts tested, leaf extracts S. angulosa, S. integrifolia, S. ocmulgee, and S. scandens were found to have strong anti-cancer activity. This study provides a basis for further mechanistic and translational studies into adjuvant therapy of malignant tumors using Scutellaria leaf tissues.