Risk of second primary malignancy (SPM) is increasing. We aimed to assess the incidence and related risk factors of SPM among breast cancer (BC) patients from this nested case-control study using the SEER database. BC patients with SPM were identified as the case group and SPM-free patients were defined as the control group. Propensity score matching of cases with controls by the year of the first primary BC diagnosis was conducted at the ratio of 1:5, and 97,242 BC patients were enrolled from 1998 to 2013 after the matching. The incidence of SPM in BC patients stratified by age groups and cancer sites was compared to the general population using the adjusted standardized incidence ratio (SIR) and the risk factors for SPM were examined using Cox proportional hazard regressions. Our study showed BC patients had excess risk for SPM than the general population (adjusted SIR for all cancer sites = 12.94, p < 0.001) and the incidence of SPM among them decreased with age. The risk of SPM was significantly related to the following demographical and clinical variables: age (40-59 vs. 18-39, HR = 1.33; 60-79 vs. 18-39, HR = 2.39; ≥80 vs. 18-39, HR = 2.84), race (black vs. white, HR = 1.12), histological type (lobular BC vs. ductal BC, HR = 1.15), radiotherapy (HR = 1.33), marital status (married vs. single, HR = 0.88) and estrogen receptor status (positive vs. negative, HR = 0.85). Consistent results were found in subgroup analysis stratified by contralateral-breast SPMs and nonbreast SPMs. © 2019 UICC.