High concentrations of acetyl polyamines have been observed in human breast cancer compared with the equivalent normal tissue, however, no explanation as to the reason for the increases has been proposed. In this study, we show that changes in the enzymes responsible for the breakdown of acetyl polyamines occur in breast cancer tissue. Spermidine/spermine N1-acetyltransferase, the first and rate-limiting enzyme in polyamine catabolism, is increased in the tumor tissue whereas polyamine oxidase (PAO) is decreased. The changes in PAO correlate with prognostic factors, and activity decreases as the size and histological grade of tumors increase. The metabolism of polyamines by PAO generates locally high concentrations of hydrogen peroxide, a known inducer of apoptosis; thus, low PAO activity may contribute to the low level of apoptosis seen in tumor cells. Therefore, drugs that induce PAO activity may be a novel means of attacking tumor cells.