Background: Although volume displacement (VD) is considered the gold standard for diagnosing breast cancer-related lymphedema, it is inconvenient. We compared bioimpedance (L-Dex) and VD measurements in a prospective cohort of breast cancer patients at risk for lymphedema. Methods: Between 2010 and 2014, a total of 223 breast cancer patients were enrolled. Following exclusions (n = 37), 186 received baseline VD and L-Dex; follow-up measurements were performed at 3–6 months intervals for 3 years. At each visit, patients fitted into one of three categories: normal (normal VD and L-Dex); abnormal L-Dex (L-Dex > 10 or increase in 10 from baseline and normal VD); or lymphedema (relative arm volume difference of >10 % by VD ± abnormal L-Dex). Change in L-Dex was plotted against change in VD; correlation was assessed using the Pearson correlation. Results: At a median follow-up of 18.2 months, 152 patients were normal, 25 had an abnormal L-Dex, and 9 developed lymphedema without a prior L-Dex abnormality. Of the 25 abnormal L-Dex patients, 4 progressed to lymphedema, for a total of 13 patients with lymphedema. Evaluating all time points, 186 patients had 829 follow-up measurements. Sensitivity and specificity of L-Dex compared with VD were 75 and 93 %, respectively. There was no correlation between change in VD and change in L-Dex at 3 months (r = 0.31) or 6 months (r = 0.21). Conclusions: VD and bioimpedance demonstrated poor correlation with inconsistent overlap of measurements considered abnormal. Of patients with an abnormal L-Dex, few progressed to lymphedema; most patients with lymphedema did not have a prior L-Dex abnormality. Further studies are needed to understand the clinical significance of bioimpedance.