Our aim was to investigate the chemopreventive potential of saffron in DMBA-induced hamster buccal pouchcarcinogenesis. Assessment was by monitoring the percentage of tumor bearing hamsters, tumor size as wellas the status of detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinomas wereinduced in the buccal pouch of Syrian golden hamsters by painting them with 0.5% DMBA in liquid paraffin threetimes a week for 14 weeks. We observed 100% oral tumor formation with severe histopathological abnormalitiesin all the hamsters treated with DMBA alone, activities of phase I and phase II detoxification enzymes, lipidperoxidation and antioxidants being significantly altered. Though oral administration of saffron completelyprevented the formation of tumors, we noticed severe hyperplasia and dysplasia in hamsters treated with DMBA,suggesting that tumors might eventually develop. Oral administration of saffron return detoxification enzymes,lipid peroxidation and antioxidants to normal ranges. The chemopreventive potential of saffron thus is likelydue to antioxidant properties and modulating effects on detoxification in favour of the excretion of carcinogenicmetabolites during DMBA-induced hamster buccal pouch carcinogenesis.