Female dogs, especially intact or neutered lately, are at increased risk for reproductive disorders including mammary tumors (MTs). This retrospective study evaluated the prevalence of reproductive pathology and associated mortality in a cohort of female dogs presented at a single veterinary clinic. The medical records of female dogs born in 2000–2003 were reviewed. The study included 599 cases, of which 293 were followed up until death. Causes of death were analyzed according to the spaying status. Among the 599 female dogs, 306 were intact (51%), 50 (8%) had been spayed before 2 years of age (ES, early spaying), and 243 (41%) after 2 years (LS, late spaying). During their lifetime, 79 dogs (13.2%) developed pyometra, and 160 (26.7%) a mammary tumor. Among the 293 dogs with complete follow-up, 103 (35.1%) had at least one MT during their lifetime, of which 53 (51.5%) died of their mammary cancer. Spayed (ES + LS) female dogs had a 4-fold decreased risk of dying from mammary cancer (OR = 0.23, 95% CI 0.11–0.47, p < 0.0001) compared to intact females. In this low-sterilization rate population, MTs developed in 35.1% of female dogs over their lifetime and was the cause of death in half of them.