Dietary sphingolipids are hydrolyzed in the intestinal tract to bioactive metabolites. In the present study, we investigated if these bioactive can suppress tumor formation, progression and metastasis in distant organs. Human cells representing early, intermediate, late and metastatic stages of breast cancer were injected into the mammary fat pad of nude mice. 0.1% of complex sphingolipids were added to the diet either before or after tumor implant to test both a preventive and an intervention approach. Orally administered sphingolipids affected tumor number and volume in a stage‐dependent manner, with the less aggressive xenografts responding with both lower tumor incidence and tumor volume while the more advanced xenografts responded with a reduction of tumor size only. This appears to correlate with the reduced rate of proliferation that was more affected in xenografts representing earlier stages of breast cancer. However, sphingolipid supplements significantly reduced metastases of MDA‐MB‐231 xenografts to the lungs (60–73%) and bone marrow (60–84%). These results suggest that sphingolipid supplements suppress less aggressive tumors and metastases while they are relatively ineffective against aggressive tumors, indicating a promising potential as chemopreventive agents.Supported by grant BCT0503453 from the Susan G. Komen Foundation and NIH/NCI R03 CA101125.