Abstract: Objective: This study presents a comprehensive quantitative evaluation of the risk of second primary malignancies (SPMs) development in patients with early-onset breast cancer exposed to radiation (age <50 years). Methods: Early-onset breast cancer patients were included from the Surveillance, Epidemiology, and End Results databases, 2000–2018. We estimated the cumulative incidence of SPMs and evaluated the associated risks of SPMs in the radiation exposure (RE) and non-radiation exposure (NRE) groups using a Poisson regression. The competitive risk model identifiedrisk factors for SPMs, constructed a nomogram, and evaluated effects and stratified risk. Results: A total of 88, 483 and 68, 085 patients were in the RE group and the NRE group, with the cumulative incidence rates of SPMs over 10 years being 3.38% and 2.62%, respectively. The relative risks of SPMs caused by radiation for patients aged 20–30, 30–40, and 40–50 was 1.10, 1.31, and 1.32, respectively. In subgroup analysis, the RE group was at a higher risk of developing SPMs than the NRE group. Among the risk factors for SPMs, exposure to radiation (HR=1.04, 95%CI: 1.01–1.12) was associated with an increased risk of SPMs. The time-dependent ROC curve of the prediction model showed that the AUC at 6, 8, and 10 years were 0.631, 0.621, and 0.607, respectively. Risk stratification divided the patients with early onset breast cancer into low-, medium-, and high-risk groups. The cumulative incidence rates in the three groups were 1.53%, 3.75%, and 7.21%, respectively (P<0.05). Conclusions: Survivors of early-onset breast cancer have a relatively high risk of SPMs development due to exposure to radiation. Monitoring efforts for these patients should be strengthened to identify high-risk patients at early stages.