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Lipedema is a painful, underdiagnosed adipose tissue disorder, characterized by symmetrical swelling of the extremities due to subcutaneous fat deposition in the buttocks, thighs, legs, and arms, sparing the most distal part of the extremities. Although etiology and pathogenesis of lipedema is unclear, possible role of hormonal and genetic factors have been proposed previously. Patients with lipedema suffer from pain, easy bruising, tenderness, and disfigurement. Pain is the leading symptom in lipedema. Since the pain is associated with depression and impaired quality of life, reduction of pain is the major therapeutic approach. Pain in lipedema is attributed to allodynia, exaggerated sympathetic signaling, and estrogens. Although the mechanism of pain in lipedema is uncertain, effective treatment of lipedema should provide a satisfactory pain reduction. Efficacy of the conservative treatment is a matter of debate. Microcannular tumescent liposuction is the most effective therapeutic option for lipedema. There is a large body of evidence that this procedure significantly reduces pain in patients with lipedema.