This study aimed to profile the characteristics of patients with colorectal cancer (CRC) with a second primary malignancy (SPM) and to identify patients with CRC at high risk of developing SPMs.We retrospectively reviewed data on patients with CRC aged 20-79 years from the Surveillance, Epidemiology, and End Results (SEER) database. Eligible patients were categorized into only one primary malignancy and SPM cohorts. A competing-risk model was used to quantify associations between SPM occurrence and the multiple traits of patients. Finally, a decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model by calculating net benefit.A total of 179,884 patients were identified, 18,285 (10.2%) of whom developed SPMs during a maximum follow-up of approximately 18 years. The median survival time after the second diagnosis was less than 4 years. The 3-year, 5-year, and 10-year cumulative risks of developing an SPM were 3.9%, 5.9%, and 10.0%, respectively. According to the multivariable competing-risk model, male colon cancer survivors, older in age, with a well-differentiated tumor and localized disease, who were treated with surgery were susceptible to SPMs. The DCA yielded a wide range of risk thresholds at which the net benefits would be obtained from our proposed model.CRC survivors remain at high risk of developing SPMs. Patients with a second diagnosis of cancer showed not only significantly worse survival but also higher cancer-specific mortality. A web-based individualized predictive tool was also provided to assist clinicians in identifying patients at high risk of developing SPMs and planning their future care management.Colorectal cancer survivors remain at high risk of developing a second primary malignancy (SPM). This study aimed to profile the characteristics of patients with colorectal cancer with second primary malignancies and to further explore the risk factors related to the development of second primary malignancies, using a large population-based cohort. A clinically useful competing-risk nomogram was developed to predict the risk of SPMs based on individual clinical factors. According to the findings, older age, male sex, white or black race, localized disease, and treatment with surgery among patients with colon cancer were associated with an increased risk of developing an SPM. These findings and the proposed tool could be useful to clinicians and caregivers in the clinical counseling of patients with colorectal cancer and the development of long-term care management.