A new type of amyloidosis, secondary to the massive deposition of beta 2-microglobulin, has been identified which is peculiar to long-term (greater than or equal to 5 years) hemodialysis. Popliteal masses have recently been described as a possible manifestation of this type of amyloidosis. We report the results of a clinical-radiologic study of the popliteal region in 28 patients (14 males, 14 females; age 52.9 +/- 12.6 years) undergoing chronic hemodialysis for 60-212 months (mean 127 +/- 40). We aimed at determining the role of diagnostic imaging (conventional radiography, ultrasonography, Computed Tomography) in this pathologic condition. Clinics detected popliteal masses in 4 patients (bilateral in 1). US allowed 2 more cases to be detected and demonstrated the cystic nature of the lesion. Ultimately, popliteal masses could be demonstrated in 6 (bilateral in 5) of 28 patients (incidence 21.4%). In the 3 patients who were investigated by CT, cysts were seen to communicate with the joint cavity (Baker's cysts). In 1 case, immunocytochemical analysis showed diffuse beta 2-microglobulin positive amyloid deposition within the synovial wall of the surgically removed cyst. All the 6 patients experienced some of the major features of dialysis-related amyloidosis: carpal tunnel syndrome (6 cases), destructive arthropathy (5 cases), carpal and shoulder bone radiolucencies (5 and 4 cases, respectively). These findings, while documenting the high prevalence of popliteal cysts among long-term hemodialysis patients and the strong correlation with dialysis-related amyloidosis, stress the importance of diagnostic imaging in the detection and follow-up of such lesions.