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The objective of this study was to determine the effect of soy-based diets on mammary tumors in female cancer- prone mice. Transgenic virgin female mice expressing human pituitary growth hormone and their respective phenotypically normal littermates were fed a diet containing either casein (C), low-isoflavone soy protein (LIS), or high-isoflavone soy protein (HIS). Indices of tumor development were measured throughout the study. Both days from birth until death and days on diet until death were increased [by 20% (P = .01) and 19% (P = .02), respectively] in the LIS group when compared with the C group. Both intervals were increased also (by 16% and 17%, respectively; P.05) in the HIS group when compared with the C group. Days from birth to first tumor were increased by 7% (P.05), as was days on diet to first tumor by 5% (P.05), in the LIS group when compared with the C group. First-onset number of tumors was decreased (P = .02) by 41% and 34% in the LIS and C groups, respectively, when compared with the HIS group. Final onset of tumors was decreased (P.05) by 44% and 9% in the LIS and HIS groups, respectively, when compared with the C group. Total area of final tumors was decreased (P.05) by 30% in the LIS group when compared with the C group. Taken cumulatively, these data suggest that a diet rich in soy protein may provide protective benefits regarding tumor development in female cancer-prone mice. Furthermore, some bioactive compounds in the HIS diet appeared to confound the soy protein-induced beneficial effects.