The mixed mammary tumor is a distinct entity in dogs, with only rare reports of similar neoplasms in man. From data now available, megestrol acetate, chlormadinone acetate, and progesterone may have a promotional effect on the occurence of canine mixed mammary tumors. These compounds—progesterone and progesterone derivatives—have marked species difference, with dogs unusually responsive. Species variability in drug metabolism and drug sensitivity and individual specific variation in target organ pathology are all important in the safety evaluation of products for human use. The facts presented herein support the contention that an increased incidence of the progestogen-dependent canine mixed mammary tumor is, in itself, of little relevance in projecting potential tumorigenesis in women.