We investigated the polyamine levels [putrescine (Put), spermidine (Spd), and spermine (Spm)] and their metabolism by simultaneously considering the ornithine decarboxylase (ODC) and diamine oxidase (DAO) activities in human colorectal cancer and in normal surrounding tissue. Single and total polyamine levels were significantly higher in the neoplastic tissue than in the surrounding mucosa from the same patients. Furthermore, the ODC activity was significantly higher and the DAO activity significantly lower in the neoplastic tissue than in the surrounding mucosa. Polyamine levels and enzymatic activities did not correlate with the clinical and histologic characteristics of patients. In normal tissue samples, no correlation was found between single and total polyamine levels and enzymatic activities (both DAO and ODC). On the contrary, in colorectal neoplastic samples, significant and positive correlations were found between the levels of total polyamines, Spd, and Spm and the ODC activity. In the same specimens, DAO activity was related to Spd levels and the Spd/Spm ratio, but, in those cases, the correlation was negative. Thus, our findings suggest that, during the neoplastic growth of the colorectal mucosa, the balance between polyamine degradation and biosynthesis is disengaged from the control exerted by the two enzymes.