Abnormal mammary gland growth is a side effect of progestin therapy in some cats. In this retrospective study, the nature and significance of morphologic changes in the mammary gland of 17 megestrol acetate (MA)-treated cats were compared to mammary lesions in 97 untreated cats. Fourteen out of 17 MA-treated cats had non-neoplastic mammary lesions including fibroepithelial hyperplasia (nine cats), lobular hyperplasia (three cats), and duct ectasia (two cats); whereas three MA-treated cats had mammary neoplasms including one adenoma and two carcinomas. Although MA has been causally linked to mammary cancer in cats, only mammary fibroepithelial hyperplasia was clearly associated with MA therapy in this study. Fibroepithelial hyperplasia occurred in older (average age 8.1 years) neutered male and female cats in the MA-treated group and in younger (average age 2.1 years) female cats in the untreated group. Morphologically, both intraductal and solid fibroepithelial growth patterns were seen. Intraductal fibroepithelial hyperplasia was further subdivided into papillary and circumferential types. An apparent greater association between MA therapy and the intraductal types of fibroepithelial hyperplasia was noted. Furthermore, it appears likely that mammary lobular hyperplasia also is linked to MA therapy. Possible mammatrophic effects of MA and other growth-promoting agents in the cat are discussed.