BACKGROUND: The higher mortality rates in patients with Systemic sclerosis (SSc) are related to SSc activity, cardiovascular disease, and neoplasms, among other factors. Our objective was to assess the impact of solid organ neoplasms (SON) and hematological neoplasms (HN) on mortality among SSc patients. METHODS: A retrospective, observational comparison of SON and HN-related deaths in SSc patients with those in the general Spanish population was conducted using data from the Spanish Hospital Discharge Database. Binary logistic regression was used to analyze the impact of SSc on mortality risk from each neoplasm. RESULTS: During 2016-2019, 139,531 in-hospital deaths from neoplasms were certified in Spain (67 in patients with SSc). Malignancies accounted for 9.7% of all deaths in SSc patients, and disease activity for 11.5% (p >
0.05). Compared to the general Spanish population, patients with SSc had a higher death ratio from lung neoplasms (18.6 vs. 25.4%, OR = 2.228, 95% CI 1.260-3.937), gynecological neoplasms (3 vs. 13.4%, OR = 4.804, 95%CI 2.372-9.730), attributable to the increased risk of uterine tumors (0.9 vs. 4.5%, OR = 6.177, 95% CI 1.931-19.758) and ovarian carcinomas (1.3 vs. 4.5%, OR = 3.456, 95% CI 1.083-11.032), and from T/NK lineage lymphomas (0.3 vs. 3.0%, OR = 8.955 95% CI: 2.181-36.767). CONCLUSION: The detection of chronic comorbidities such as cancer is emerging as a noteworthy component of standard care for SSc patients. This can be addressed during their follow up or even in specific screening programs aimed at achieving better long-term quality of life and prognosis.