AIM: Aberrant epigenetic events are important contributors to the pathogenesis of different types of cancers and dietary botanicals with epigenetic properties can influence early cancer development leading to cancer prevention effects. We sought to investigate potential combinatorial effects of bioactive dietary components including green tea polyphenols (GTPs) and broccoli sprouts (BSp) on neutralizing epigenetic aberrations during breast tumorigenesis. MATERIALS & METHODS: The combinatorial effects were evaluated in a breast cancer transformation cellular system and breast cancer mouse xenografts. RESULTS & CONCLUSION: Combined treatment with epigallocatechin-3-gallate in GTPs and sulforaphane in BSp resulted in a synergistic inhibition of breast cancer cellular growth. Further studies revealed this combination led to genome-wide epigenetic alterations. Combinatorial diets significantly inhibited tumor growth in breast cancer mouse xenografts. Collectively, these studies indicate that combined GTPs and BSp are highly effective in inhibiting early breast cancer development by, at least in part, regulating epigenetic mechanisms.