Clinical and epidemiological evidence has recently revealed a link between coronary artery disease (CAD) and cancer. Shared risk factors and common biological pathways are probably involved in both pathological conditions. The aim of this paper was to evaluate whether and which conventional risk factors and novel circulating biomarkers could predict cancer incidence and death in patients with CAD. The study included 750 CAD patients, who underwent blood sampling for the evaluation of systemic inflammatory indexes (NLR and SII) and specific biomarkers of oxidative damage (leukocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)). Study participants were followed up for a mean of 5.4 ± 1.2 years. Sixty-seven patients (8.9%) developed cancer during the follow-up time, and nineteen (2.5%) died of cancer. Cox multivariable analysis revealed that age (HR = 1.071; 95% CI: 1.034–1.109;p< 0.001), smoking habit (HR = 1.994; 95% CI: 1.140–3.488;p= 0.016), obesity (HR = 1.708; 95% CI: 1.022–2.854;p= 0.041) and SII (HR = 1.002; 95% CI: 1.001–1.003;p= 0.045) were associated with cancer incidence, while only age (HR = 1.132; 95% CI: 1.052–1.219;p= 0.001) was a predictor of cancer death. Patients with lung and gastrointestinal cancers had significantly higher median mtDNAcn levels than those without cancer. Our study suggests that aggressive risk factor modification and suppression of chronic inflammation may be essential to preventing cancer in CAD patients.