Nicotinamide (NA), a naturally occurring vitamin and a protease inhibitor, has been shown to be effective in treating some skin ailments. It inhibits cell proliferation and induces cell differentiation. This report shows the effects of NA on mouse skin tumor development and on the critical events involved in this process. NA reduced tumor growth, inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ornithine decarboxylase activity, but induced the transglutaminase activity which was inhibited by TPA under different experimental conditions. The effects of NA on ornithine decarboxylase (ODC) and transglutaminase (TG) indicated that nicotinamide (NA) probably programmed the cells for their death in the natural course of time, i.e. programmed cell death. This observation indicates that NA might be a better agent for the detailed study and for the better use in prevention of cancer alone or in combination with other drugs.