Expression of the p27kip1 cell cycle inhibitor is downregulated in a wide range of carcinomas, yet it is rarely inactivated completely. Our recent studies of a mouse model of prostate carcinogenesis have revealed that cancer progression is enhanced by a two-fold reduction in p27kip1 gene dosage, but is unexpectedly inhibited by further decrease in p27kip1 activity. This paradoxical finding may explain the unusual features of p27kip1 downregulation in human cancer, and also suggests a potential route for therapeutic intervention.