BACKGROUND/AIM: Methionine inhibits proliferation of breast and prostate cancer cells. This study aimed to determine cell cycle effects of methionine and selectivity for cancer cells. MATERIALS AND METHODS: MCF-7 (breast), LNCaP (prostate), and LS-174 (colon) cancer cells (wild-type p53), DU-145 (prostate) and SW480 (colon) cancer cells (mutated p53), and immortalized, non-tumorigenic MCF-10A (breast), BPH-1 (prostate), and NCM-460 (colon) epithelial cells were used. Cell cycle effects were assessed by flow cytometry and cell cycle-related gene expression by microarray analysis and QRT-PCR. RESULTS: L-Methionine at 5 mg/ml for 72 hours (non-apoptotic) arrested cell cycle in LNCaP, DU145, and MCF-7 cells, but not in untransformed cells, nor in LS-174 cells. LNCaP and MCF-7 cells were arrested at G(1), but DU-145 at S. Methionine up-regulated CDKIs and down-regulated CDKs. CONCLUSION: L-Methionine selectively inhibits proliferation of breast and prostate cancer cells, but not non-tumorigenic cells, and may thus have therapeutic benefits. p53 status appeared to determine the cell cycle stage at which methionine acts.