Lymphoscintigraphy was used to measure lymphatic function at rest and during exercise in breast cancer survivors with lymphedema (BCRL, n = 10), breast cancer survivors (BC, n = 10), and controls (Cont, n = 10). After injection of (99m)Tc-antimony colloid to the hands, subjects rested or performed 12 repeated sets of arm cranking for 2.5 min at 0.6 W/kg followed by 2.5 min of rest. One-minute spot views were taken with a gamma-radiation camera immediately postinjection and every 10 min over 60 min to calculate clearance rate. As well, an upper body scan was taken at 65 min postinjection to measure radiopharmaceutical uptake in the axilla (Ax) and forearm (Fore). All groups displayed similar increases in clearance rate with exercise (P = 0.000). Ax significantly increased with exercise in Cont only [Cont: (mean +/- SD) 4.9 +/- 2.6 vs. 7.9 +/- 4.2%, P = 0.000; BCRL: 1.4 +/- 1.2 vs. 1.7 +/- 2.1%, P = 0.531; BC: 3.9 +/- 3.4 vs. 5.2 +/- 3.2%, P = 0.130], whereas Fore, indicating dermal backflow, significantly increased in BCRL only (BCRL: 2.4 +/- 0.87 vs. 4.4 +/- 2.0%, P = 0.004; BC: 1.1 +/- 0.25 vs. 1.1 +/- 0.31%, P = 0.784; Cont: 0.93 +/- 0.26 vs. 1.0 +/- 0.20%, P = 0.296). The results indicate that, in women with BCRL, exercise causes radiopharmaceuticals to clear from the hand at the same rate as BC and Cont, but, instead of reaching the axilla, a greater amount of activity gets trapped in the dermis of the forearm. BC, meanwhile, have similar lymphatic function as Cont; however, there is a highly variable response that may suggest that some BC subjects may be at risk for developing lymphedema.