The aim of this study was to determine whether inflammation is related to cancer development, and whether the incidence of cancer is increased and occurs in a site-specific manner in patients with systemic autoimmune rheumatic diseases (SARDs).This study included a nationwide dynamic cohort of patients with various newly diagnosed SARDs from 1997 to 2010 with follow-up until 2012.This study included 75,123 patients with SARDs. During 562,870 person-years of follow-up, 2844 patients developed cancer. Between 1997 and 2010, the highest number of newly diagnosed SARDs cases were rheumatoid arthritis (n = 35,182), followed by systemic lupus erythematosus (SLE, n = 15,623), Sjögren syndrome (n = 11,998), Kawasaki disease (n = 3469), inflammatory bowel disease (n = 2853), scleroderma (n = 1814), Behçet disease (n = 1620), dermatomyositis (n = 1119), polymyositis (n = 811), and vasculitis other than Kawasaki disease (n = 644). A significant standardized incidence ratio (SIR) of overall cancer was observed for patients with SLE (1.41; 95% confidence interval [CI], 1.28-1.56), Sjögren syndrome (1.19; 95% CI, 1.08-1.30), scleroderma (1.27; 95% CI, 1.02-1.59), dermatomyositis (4.79; 95% CI, 4.01-5.73), polymyositis (1.47; 95% CI, 1.05-2.06), vasculitis excluding Kawasaki disease (1.75; 95% CI, 1.20-2.55), and Kawasaki disease (2.88; 95% CI, 1.60-5.20). Overall, patients with most SARDs had a significantly higher risk of inflammation-associated site-specific cancers and hematologic malignancies.This study confirms that autoimmunity is associated with site-specific and hematological malignancies and provides clinical evidence of an association between inflammation and subsequent site-specific cancer development. These findings support the importance of inflammation in site-specific organ system carcinogenesis.