Why is pain an essential aspect of the definition of LiDo? Areas of the body affected by lipohyperplasia dolorosa (LiDo, “lipedema”) are described as painful. Pain is an essential symptom for differential diagnosis because pain is absent in phenotypically overlapping diseases. However, the understanding of pain in general, its underlying mechanisms, and its consequences is undergoing significant changes. Therefore, a better understanding of pain is required to diagnose pain, and it holds great potential to shape LiDo pain into a decisive diagnostic criterion, elucidate its physiological causes, and develop new LiDo-specific pain therapies.