A growing body of evidence indicate that carotenoids possess anticarcinogenic, anti-mutagenic and immunomodulating effects. Saffron obtained from the dried stigmas of Crocus sativus L., is an important spice, rich in carotenoids, consumed commonly in different parts of the world. Our laboratory first reported the anticancer activity of saffron extract (dimethyl-crocetin) against a wide spectrum of murine tumors and human leukemia cell lines. The present report reviews the role of saffron in serving as a chemopreventive agent in modifying cancer risk. Dose-dependent cytotoxic effect to carcinoma, sarcoma and leukemia cells in vitro were noted. Saffron delayed ascites tumor growth and increased the life span of the treated mice compared to untreated controls by 45-120%. In addition, it delayed the onset of papilloma growth, decreased incidence of squamous cell carcinoma and soft tissue sarcoma in treated mice. Understanding the mechanisms of action of saffron have been solitarily based on their carotenoid-like action. Our results indicated significant inhibition in the synthesis of nucleic acids but not protein synthesis. It appears now that saffron (dimethyl-crocetin) disrupts DNA-protein interactions e.g. topoisomerases II, important for cellular DNA synthesis.