Epidemiological evidence associating the decreased risk of prostate cancer with frequent consumption of tomato products inspired us to conduct a small intervention trial among patients diagnosed with prostate adenocarcinoma. Tomato sauce pasta was consumed daily for 3 weeks before their scheduled prostatectomy, and biomarkers of tomato intake, prostate cancer progression and oxidative DNA damage were followed in blood and the available prostate tissue. The whole food intervention was so well accepted by the subjects that the blood lycopene (the primary carotenoid in tomatoes responsible for their red color) doubled and the prostate lycopene concentration tripled during this short period. Oxidative DNA damage in leukocytes and prostate tissues was significantly diminished, the latter mainly in the tumor cell nuclei, possibly due to the antioxidant properties of lycopene. Quite surprising was the decrease in blood prostate-specific antigen, which was explained by the increase in apoptotic death of prostate cells, especially in carcinoma regions. Prostate cancer cell cultures (LNCaP) were also sensitive to lycopene in growth medium, which caused an increased apoptosis and arrested the cell cycle. A possible explanation of these promising results may reside in lycopene effects on the genes governing the androgen stimulation of prostate growth, cytokines and on the enzymes producing reactive oxygen species, all of which were recently discovered by nutrigenomic techniques. Other phytochemicals in tomato may act in synergy with lycopene to potentiate protective effects and to help in the maintenance of prostate health.