Chronic hemodialysis has led to the prolongation of life in many patients with end-stage renal disease, but has also allowed for the development of new diseases that are a consequence of this clinical setting. B2-microglobulin accumulation leading to systemic amyloidosis may be the most recent disease in this category. This case report documents the development of bilateral popliteal tumors in a patient undergoing chronic hemodialysis for 9 years. Removal of one of the tumors and pathological examination demonstrated amyloid that was positive for B2-microglobulin by specific antibody testing. This case adds further support to the suggestion that B2-microglobulin amyloidosis in chronic hemodialysis patients is truly a systemic disorder. The development of popliteal tumors, particularly in proximity to joints, in a chronic hemodialysis patient, must include amyloidosis in the differential diagnosis.