Background: Methionine inhibits proliferation of breast and prostate cancer cells. Here, we determined the influence of L-methionine on functional molecular signatures in these cell lines. Methods: MCF-7 and LNCaP cells were treated with L-methionine (5 mg/ml) for 72 h. Changes in molecular signatures of these cells were examined by microarray analysis of 15,814 probes in triplicate experiments. Results: In LNCaP cells, 325 genes were up-regulated by methionine, and 517 genes down-regulated. In MCF-7 cells, 86 genes were up-regulated and 135 genes down-regulated. Ninety-eight genes were regulated in the same direction by methionine in both cells lines, and five other genes were changed in expression in opposite directions. Conclusion: Several of the up-regulated genes encode proteins involved in cellular redox regulation, suggesting that methionine may enhance antioxidant mechanisms. Many of the down-regulated genes belong to protein kinase families that may be related to the anti-proliferative effects of methionine on breast and prostate cancer cells. © Springer-Verlag 2010.