Phytochemical investigation of the stem bark of Xylopia pierrei Hance led to the isolation of one triterpene, polycarpol (1), three heptenes, (7R)-acetylmelodorinol (2), (7R)-melodorinol (3), and melodienone (8), and four flavonoids, pinocembrin (4), isochamanetin (5), chrysin (6), and dichamanetin (7). All compounds were isolated for the first time from this plant species. The structures of the isolated compounds were characterized by spectroscopic techniques and by comparison of the spectroscopic data with the literature values and the stereochemistry at the asymmetric carbon was determined by the modified Mosher's method. Among them, compound 2 displayed potent cytotoxic activity against human small cell lung cancer (NCI-H187) cells with an IC50 value of 6.66 mu M and it was 2.3-fold higher than that of the reference anticancer drug, ellipticine. In addition, compound 2 was also evaluated against the non-cancerous Vero cells and showed high selectivity index of 8.89, which is 59-fold greater than that of ellipticine. The findings suggest that compound 2 should be further developed as a potential lead molecule for anticancer drug development.