Experiments reported herein tested the hypothesis that cultivars of apple (Malus domestica Borkh.) would demonstrate anticancer activity in vivo as predicted by in vitro measures. Freeze dried powders of Red Delicious (RD), Fuji (FJ), Golden Delicious (GD), and Granny Smith (GS) apple cultivars were evaluated. Significant differences were noted among cultivars in total phenolics (P < 0.0001), flavonoids (P < 0.0003), oxygen radical absorbance capacity (P < 0.0001), and growth inhibition in the MDA-MB-468 human breast cancer cell line relative to vehicle-treated cells (P < 0.0001). These findings were extended to predict inhibition of the postinitiation phase of 1-methyl-1-nitrosourea-induced mammary carcinogenesis by freeze-dried whole apple powders of the same cultivars. Although rats fed apple-containing diets did not have lower incidence or multiplicity of cancers than rats fed control diet, a finding consistent with epidemiological reports on fruit and breast cancer risk, differences among cultivars were noted, with the greatest difference in cancer multiplicity between GS and RD (1.46 vs. 2.47 cancers/rat; P = 0.0159). The rate of cell proliferation in mammary carcinomas differed between GS and RD (P < 0.001), whereas the apoptotic rate did not. These findings suggest altered methodology for screening apples for anticancer activity and that more diverse apple cultivars with higher phytochemical content should be evaluated.