Malignant cell proliferation is associated with an increase intracellular polyamine metabolism which itself appears to be in equilibrium with the extracellular circulating polyamine compartments. Erythrocyte polyamine contents may be used clinically as an index of cell proliferation, but the exact biological roles of circulating polyamines, considered as physio(patho)logical parameters involved in the homeostatic(dys)regulation of cell proliferation, remain obscure. It is known that circulating polyamines help promote malignant cell proliferation and metastatic dissemination, but their ultimate targets are not yet completely understood. Either produced by actively proliferating normal or cancer cells, or absorbed from the gastro-intestinal tract (food and colonic microfloral population), circulating polyamines could favour in vivo malignant cell proliferation. 1) Since these organic polycations are more rapidly internalized by cancer cells than by normal ones, do they join and facilitate the malignant intracellular polyamine metabolism? 2) Does binding of polyamines to specific acceptor sites at the surface of cancer cells, thereby modulating endocytosis of biological factors present in the extracellular spaces, modify the homeostatic control of cell proliferation and differentiation? 3) Do modifications of blood polyamine compartmentalization, observed in cancerous organisms, responsible for new enzyme and/or immune capacities, contribute to tumor progression? Answering the above-mentioned questions would lead to new therapeutic approaches in human oncology.