The present study investigated the influence of dietary omega-3 fatty acid supplementation on the growth of human colon carcinoma xenograft in athymic nude mice. Four diets were fed to evaluate the effect of levels and types of fat on colon tumor growth. Animals were maintained on a standard diet modified by addition of fats containing omega-3 and omega-6 fatty acids to represent high and low fat intakes for 53 days. The final mean estimated tumor weight for the high fat corn oil (24%) fed group was 2,302 mg, whereas the low fat (8% corn oil) group was 1,681 mg. The final mean tumor weight of the high fat menhaden oil fed group was 782 mg representing a 66% decrease in growth compared to the high fat corn oil group and a decrease of 54% compared to the low corn oil fed group. The high fat golden algae oil fed group resulted in a mean final tumor weight of 223 mg representing a 90% inhibition of tumor growth relative to the high fat corn oil fed group and 87% inhibition of growth compared to the low fat corn oil fed group. These findings indicate that dietary omega-3 fatty acids possess significant tumor suppressing properties and that the primary tumor suppressing fatty acid is docosahexaenoic acid. Histopathologic examination of control and treated tumors and expression array analyses (human cytokine and apoptosis arrays) support the tumor growth inhibition data and provide evidence for discussion of possible mechanisms for the observed growth inhibition.