Cancer is a common event in patients with rheumatic diseases. In some cases, the disease, its risk factors, or its treatment could play a role in favoring cancer. This article analyzes the current knowledge on the risk of malignancy associated with biologics in rheumatic diseases and discusses some methodological issues to be considered when evaluating the association between disease, treatments, and the risk of cancer. This article focuses on the risk of overall malignancy but also of skin cancer, lymphoma, and recurrent cancer associated with all biologics marketed for the treatment of rheumatic diseases.