Three natural cembranoids from the Red Sea soft coral Sarcophyton glaucum namely (1 S,2 E,4 R,6 E,8 R,11 S,12 R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1 S,2 E,4 R,6 E,8 S,11 R,12 S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1 S,4 R,13 S)-cembra-2 E,7 E,11 E-trien-4,13-diol were evaluated for their inhibitory effects on mouse melanoma B16F10 cell growth. Results show that all the cembranoids strongly inhibit viability of melanoma cells particularly during 48–72 hrs treatment and also inhibit de novo DNA synthesis and PARP activity and stimulate fragmentation of DNA. (1 S,2 E,4 R,6 E,8 R,11 S,12 R)-8,12-epoxy-2,6-cembradiene-4,11-diol was not cytotoxic to monkey kidney CV-1 cells at the concentration that produces the anti-melanoma effects which indicates that this compound may be a good candidate for further development. (1 S,2 E,4 R,6 E,8 S,11 R,12 S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1 S,4 R,13 S)-cembra-2 E,7 E,11 E-trien-4,13-diol were found to be cytotoxic to healthy cells.