Abstract Purpose The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. Methods We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase–control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. Results TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10–0.89), as were intermediate (OR 0.18 IC 0.07–0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03–0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08–2.36; OR 1.48 IC 1.09–2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15–2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22–2.11) and HER2+ (OR 1.59 IC 1.03–2.45) tumors. Conclusion Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.