Mammalian ornithine decarboxylase and histidine decarboxylase present common structural and functional features, and their products also share pharmacological and physiological properties. Although accumulated evidence pointed for years to a direct involvement of polyamines and histamine in tumour growth, it has been only in the last few years that new molecular data have contributed to the clarification of this topic. The aim of this commentary is to review the molecular grounds of the role of histamine and polyamines in cancer and to point to possible directions for future research in emerging areas of interest.