Lipedema is a disease with high prevalence but low recognition. It is often misdiagnosed and underdiagnosed. Obesity and lymphoedema are the most common differential diagnoses and can also coexist in patient with lipedema. Its broad range of presentation and fat distribution types contribute to this confusion. It is likely that lipedema symptom variations and presentation forms are often associated with hormonal variations, chronic low-grade systemic inflammation, and wide polygenic variations. This paper presents a theory regarding the clinical evolution of lipedema clinical and its involvement with other diseases, suggesting a three-phase approach for treatment.