Background: A previous study reported a new ultrasonography (US) measurement technique to evaluate the cross-sectional area (ΔCSA) of lymphedema in the upper extremity. This ΔCSA correlated well with parameters, such as the circumference, volumetry, and bioimpedance analysis (BIA) in healthy people and upper extremity lymphedema patients. This study examined whether a US measurement technique is clinically useful in patients with lymphedema in the lower extremity. Methods and Results: Forty patients diagnosed with unilateral lower extremity lymphedema were enrolled in this study. The subjects' leg circumference, BIA, isokinetic strength, and ΔCSA were examined on the same day. The leg circumference was measured at 15 cm above the knee (AK) and below the knee (BK) crease using a tape measure. BIA was performed by a trained physical therapist, and the data of impedance (Z) at 1 and 5 kHz of each side of the lower limbs and extracellular water (ECW) were used. A fully experienced physician measured soft tissue thickness, the distance between the skin and the fascia of the muscle, three times each at the anterior, medial, posterior, and lateral aspects of the bilateral legs by US at 15 cm AK and BK. The amount of soft tissue in the ΔCSA was calculated using the designed formula from the mean values of the thicknesses. Each parameter was calculated as the ratio of the sound side to the lesion side. The Pearson and Spearman correlation coefficients were used to assess the significance of these parameters. The ratio of ΔCSA measured at 15 cm AK and BK showed strong positive correlations with the circumference difference at the same level (rho = 0.790, p = 0.000, and rho = 0.882, p = 0.000, respectively). In addition, it showed moderate or strong correlations with the ratio of Z at 5 and 1 kHz in the BIA of the lower limbs (AK15, r = -0.511, p = 0.001 and r = -0.497, p = 0.001; BK15, r = -0.780, p = 0.000 and r = -0.756, p = 0.000, respectively). Although ECW and body mass index showed weak positive correlations with the ratio of ΔCSA measured at 15 cm BK, there was no significant correlation between the ratio of ΔCSA and the isokinetic muscle strength. Conclusion: The ΔCSA results showed moderate-to-strong correlations with other conveniently used methods except for the isokinetic muscle strength. As the US ΔCSA technique could measure lymphedema status with a structural consideration, it could also be recommended as a conventional measurement method in patients with upper and lower extremity lymphedema.