Lymphedema is a chronic, progressive disease affecting millions of people worldwide, but it is often overlooked. Protein-rich fluid accumulates in the interstitial space due to either primary congenital disease or secondary damage to the lymphatic system, often associated with surgeries or cancer treatments. Comparing and contrasting the presentation of lymphedema-related lower extremity swelling with other etiologies and clinical presentations will illuminate accurate differential diagnosis. Timely diagnosis of lymphedema and proper management are key to avoiding loss of function, disfigurement, pain, and decreased quality of life.