The ginger rhizome is rich in bioactive compounds, including -gingerol, -gingerol, and -gingerol; however, to date, most research on the anti-cancer activities of gingerols have focused on -gingerol. In this study, we compared -gingerol with -gingerol and -gingerol in terms of their ability to inhibit the growth of human and mouse mammary carcinoma cells. A colorimetric assay based on the enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide revealed that -gingerol was more potent than -gingerol and at least as potent as -gingerol for the inhibition of triple-negative human (MDA-MB-231, MDA-MB-468) and mouse (4T1, E0771) mammary carcinoma cell growth. Further investigation of -gingerol showed that it suppressed the growth of estrogen receptor-bearing (MCF-7, T47D) and HER2-overexpressing (SKBR3) breast cancer cells. The inhibitory effect of -gingerol on the growth of MDA-MB-231 cells was associated with a reduction in the number of rounds of cell division and evidence of S phase-cell cycle arrest, as well as induction of apoptosis due to mitochondrial outer membrane permeabilization and the release of proapoptotic mitochondrial cytochrome c and SMAC/DIABLO into the cytoplasm. Surprisingly, killing of MDA-MB-231 cells by -gingerol was not affected by a pan-caspase inhibitor (zVAD-fmk) or an anti-oxidant (N-acetylcysteine), suggesting that the cytotoxic effect of -gingerol did not require caspase activation or the accumulation of reactive oxygen species. These findings suggest that further investigation of -gingerol is warranted for its possible use in the treatment of breast cancer.