Objective: Emerging data have shown an increased risk of malignancy among patients diagnosed with systemic sclerosis (SSc) so identification of risk factors linking both disorders might have prognostic implications. The aim of this study was to assess the clinical and treatment-related risk factors for cancer in a single-center cohort of patients with SSc. Methods: Demographic, clinical, capillaroscopic, immunological and treatment-related data from 432 consecutive SSc patients were retrospectively analyzed. Variables that reached significant association in the univariate analysis were entered into a logistic regression in order to identify independent risk factors for cancer. Results: Malignancy was diagnosed in 53 patients (12.2%). Fifty-eight neoplasms were identified, among which breast (n = 15), lung (n = 10) and hematologic (n = 9) malignancies were the most prevalent. In 19 patients the diagnosis of both scleroderma and tumour was made in b3 years apart. Cancer significantly decreased the probability of survival (OR = 2.61; 95% CI 1.46-4.69; p = 0.001). No association with age, sex, smoking, cutaneous subset or RNA polymerase-III antibodies was found. However, risk of cancer was directly associated with the presence of anti-PM/Scl antibodies (OR = 3.90; 95% CI 1.31-11.61; p = 0.014), and inversely related to aspirin use (OR = 0.33; 95% CI 0.12-0.90; p = 0.031), which remained as independent risk factors for cancer on multivariate analysis. Conclusions: PM/Scl antibodies seemto be associated with a higher risk of cancer in scleroderma. In contrast, the use of aspirin is related to a lower risk of cancer in our series. More studies are needed to ascertain the role of anti PM/Scl antibodies and aspirin in the development of malignancy among patients with SSc. (C) 2017 Elsevier B.V. All rights reserved.