Osteoarticular symptoms and signs, such as carpal tunnel syndrome, periarthritis humeroscapularis, synovial and joint inflammation, lead to the clinical diagnosis of beta 2-microglobulin (beta 2-M) amyloidosis. Radiologically, destructive arthropathy, spondylarthropathy and periarticular cystic bone radiolucencies can be demonstrated by plain X-ray and conventional and computed tomography. Magnetic resonance is used to visualize amyloid masses in special locations such as the cervical spine. Joint ultrasonography demonstrating thickening of synoviae and tendons has become a useful non-invasive diagnostic tool, although it is not specific for beta 2-M amyloidosis, and results depend on observer experience. Efforts to develop more specific methods for demonstration of amyloid deposits have led to two scintigraphic techniques based on the injection of radiolabelled proteins which are incorporated into the amyloid tissue. One method uses serum amyloid P component, a non-specific constituent of all types of amyloid. An alternative imaging technique based on radiolabelled beta 2-M as the specific precursor molecule of beta 2-M amyloidosis appears to be a more sensitive diagnostic method. Both tracer techniques have been used so far only in small single-centre clinical studies, and a more widespread application will require the introduction of recombinant material as the protein source for labelling. The 'gold standard' for the definitive diagnosis of beta 2-M amyloidosis, and also for reference in the evaluation of new diagnostic techniques, remains the histomorphological demonstration of beta 2-M amyloid by Congo red staining, green birefringence under polarized light, positive immunostaining with anti-beta 2-M antibodies, and electronoptic visualization of amyloid fibrils in tissue obtained invasively by biopsy, surgery or autopsy.