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OBJECTIVE. The objective of our study was to examine the frequency and significance of visualization of popliteal nodes during lymphoscintigraphy for the investigation of lower extremity swelling. MATERIALS AND METHODS. Technetium-99m–labeled nanocolloid was injected subcutaneously in the first web spaces of both feet of 204 consecutive patients (69 males, 135 females; age range, 11–79 years) undergoing routine, clinically indicated lymphoscintigraphy; imaging was performed 5, 45, and 150 minutes after injection. The patients were asked not to undertake any vigorous exercise between the injection and completion of imaging. RESULTS. No popliteal nodes were visualized in 29 patients in whom there was no evidence of lymphedema on clinical or lymphoscintigraphic examination (group 1). Unilateral or bilateral popliteal nodes were visualized in 10 of 39 patients (25.6%) with clinical evidence of lymphedema but normal lymphoscintigraphy findings (group 2) (p < 0.005 vs group 1). In 136 patients with clinical evidence of lymphedema and abnormal lymphoscintigraphy findings (group 3), unilateral or bilateral popliteal nodes were visualized in 59 (43.4%) (p < 0.0001 vs group 1). Popliteal nodes were visualized in 40 of 73 limbs with “dermal backflow” (54.8%) and 42 of 335 limbs without dermal backflow (12.5%) (p < 0.0001). CONCLUSION. Popliteal node visualization after subcutaneous foot web space injection is an important sign of abnormal lymphatic function in patients with clinical lymphedema of the lower extremities.