Epigenetic changes are stable modifications of DNA or histones that profoundly alter gene expression. They can be changed by environmental influences and can then be passed on to daughter cells or via the germ line to offspring. A variety of changes in epigenetic marks and in the expression of noncoding RNA has been found in cancer as well as in chronic inflammatory diseases. Interestingly, in both diseases similar mechanisms and pathways are affected albeit often to a different extent. DNA methylation is often lost in repetitive sequences, while in promoter regions hypo- as well as hypermethylation is found. Changes in microRNA levels typically affect microRNAs that are changed by an inflammatory environment, but disease specific changes have also been found in the blood and various cell types of patients with rheumatoid arthritis, systemic lupus erythematosus and other rheumatic diseases. Therefore, changes in the expression of microRNA in particular, but also demethylated gene loci, have been proposed as potential biomarkers in chronic inflammatory diseases and in cancer. Potentially, these changes could be used for early diagnosis and also to predict treatment response. Unfortunately most studies in rheumatology up to now were not designed to validate these epigenetic changes as biomarkers. Since the cancer field is much more advanced in the usage of biomarkers for disease subclassifications and subsequent therapeutic decisions, it is worthwhile to take a closer look at the biomarkers, methods and procedures used in oncology and to see which of these could also be applied to predicting disease severity and therapeutic response in rheumatic diseases. This article will highlight common epigenetic pathways activated in cancer and various rheumatic diseases and summarise epigenetic changes that have the potential to become biomarkers in rheumatic diseases.