Comorbidities can, but need not be causally related to the primary disease in the sense of a consequential disease. Since there are both slim LiDo patients and obese women without “lipoedema”, obesity in LiDo is considered coincidental. Lipohyperplasia dolorosa (LiDo) is a disproportionate, bilateral, and symmetrical accumulation of subcutaneous fat tissue in the lower and upper extremities. The fat pads extend to the ankles/wrists, while feet and hands are spared, leading to the characteristic cuff sign. In contrast to obesity, patients suffer from pain in the extremities, sensitivity to palpation, and a tendency to bruising. The adipose tissue in the affected areas consists of hypertrophic and hyperplastic adipocytes. While the former shrink under diet and exercise or after bariatric surgery and the obesity improves, in LiDo, painlessness can only be achieved through surgical removal, i.e., numerical reduction of the hyperplastic cells. Obesity worsens the morphological signs and sometimes the symptoms, too, of LiDo and promotes the development of secondary lymphoedema in “lipoedema”. Inflammation, insulin resistance, and increased, partly insulin-triggered oestradiol production in subcutaneous adipose tissue accelerate morbidity in lipohyperplasia dolorosa. Therefore, an anti-inflammatory and weight-reducing diet and exercise are mainstays of lipoedema therapy both from a hormonal and lymphological perspective.