Diethylnorspermine is the structural analog of polyamines. Polyamines were shown to downregulate polyamine synthesis and uptake, upregulate polyamine catabolism, and result in a profound depletion of polyamines. Diethylnorspermine is adenosylmethionine decarboxylase, ornithine decarboxylase inhibitor and spermidine-spermine N1-acetyltransferase stimulant. Diethylnorspermine is under investigation as a novel anticancer drug for a variety of neoplasms. It has sustained inhibitory effects on the growth of human prostate carcinoma cells in vitro as well in vivo. This polyamine analog may provide a new tool in the chemotherapy of prostate cancers with various phenotypes. Diethylnorspermine was relatively well tolerated in patients with advanced hepatocellular carcinoma (HCC) including those with mild-to-moderate liver dysfunction but further evaluation of diethylnorspermine monotherapy for advanced HCC does not appear to be justified because of insufficient evidence of clinical benefit in the patients evaluated in this study. Also, no evidence of clinical activity was detected in metastatic breast cancer treatment (phase II clinical study).