The current study was aimed to explore the anti-cancer potential of lyngbyabellin-B against SkBr3 and T-47D breast cancer cells. The study demonstrated that treatment of SkBr3 and T-47D cells with lyngbyabellin-B significantly suppressed viability in dose-dependent manner. Treatment of SkBr3 and T-47D cells with lyngbyabellin-B for 48 h led to reduction in migration in both the cell lines. Adhesion of the cells to collagen IV coated wells was significantly reduced in SkBr3 and T-47D cells on treatment with lyngbyabellin-B. In SkBr3 and T-47D cells treatment with lyngbyabellin-B reduced invasion to 53 and 58%, respectively. Western blotting analysis showed that treatment of SkBr3 and T-47D cells with lyngbyabellin-B reduced expression of MMP-2 and MMP-9. Treatment of SkBr3 and T-47D cells with lyngbyabellin-B led to significant increase in cell apoptosis. In SkBr3 and T-47D cells lyngbyabellin-B treatment led to elevation of Bax expression with subsequent lowering of Bcl-2 level. The expression of caspase-3 was promoted and PARP cleavage increased on treatment with lyngbyabellin-B in SkBr3 and T-47D cells. In SkBr3 and T-47D cells, lyngbyabellin-B treatment caused decrease in STAT3 phosphorylation compared to the control cells. Therefore, lyngbyabellin-B may be developed as potential candidate for treatment of breast cancer.