Background: Bioimpedance spectroscopy (BIS) measurements of breast lymphedema poses practical and technical challenges, in particular the determination of the resistance at zero frequency (R0), the index of change in breast lymph content. Conventionally, R0 is calculated from data analysis by using a procedure eponymously known as Cole modeling, a method that is error-prone in the breast. The aim of this study was to evaluate polynomial curve fitting as an alternative analytic procedure. Methods and Results: A sub-set of breast BIS measurements from 41 women with self-ascribed breast lymphedema obtained as part of the Breast Edema Exercise Trial (BEET) were analyzed by both the Cole and polynomial methods. BIS files for all subjects were able to be analyzed by using the polynomial method but only 73% and 88% of data files were analyzed for the affected and unaffected breasts, respectively, by using the Cole method. For those files that were capable of being analyzed by both methods, R0 values were highly correlated (r = 0.99) but with a small (1.6%) although statistically significant difference (paired t test, p < 0.001) between methods. Conclusions: Analysis of BIS data using polynomial curve fitting is an acceptable and robust alternative to Cole modeling, particularly where impedance measurements are susceptible to technical sources of error of measurement. The small magnitude of difference observed between methods is unlikely to lead to misclassification of patients with lymphedema based on BIS assessment.