Histopathological evaluation of the synovial membrane is of little significance in diagnosing systemic connective tissue disorders in view of the absence of microscopic features specific for particular diseases and clinical criteria, radiological examinations and serological tests used in clinical practice. Histopathological features similar to those present in rheumatoid arthritis (RA) are also found, although they occur less prominently, within the synovial membrane in the course of spondyloarthropathy, systemic lupus erythematosus and in systemic sclerosis. Histopathological evaluation of the synovium is more important in the differential diagnosis of arthritis of other aetiology, such as tuberculosis or neoplastic changes. It should be noted, however, that histopathological and immunohistochemical studies of the synovial membrane have contributed to a better understanding of cellular and molecular pathogenetic mechanisms in RA and in other rheumatic disorders. The possibility of using small arthroscopic biopsies is currently being considered to assess the efficacy of targeted therapy in rheumatic diseases.