OBJECTIVE: This study aimed to evaluate adipose tissue of lipedema patients. METHODS: Gluteo-femoral (affected area) and interscapular (nonaffected area) adipose tissue from 10 lean patients affected by lipedema stage 1 to 2 was studied and compared with tissue from 10 patients with obesity and 12 lean patients. RESULTS: The main features were alterations of capillaries with wall thickening (p ≤ 0.0001), endothelial and pericyte hyperplasia (p = 0.03 and p = 0.004), hypodense areas in basal membrane, and endothelial degeneration with exfoliation of degenerated cells into the capillary lumen. Adipocytes were larger (hypertrophic) in affected (P ≤ 0.0001) and nonaffected (p = 0.0003) areas compared with those with obesity and who were lean (both p ≤ 0.0001). Frequently the cytoplasm of adipocytes contained massive deposition of calcium crystals as revealed by Von Kossa staining (p = 0.023) and electron microscopy. CD68 immunoreactive macrophages were more abundant in affected areas (p = 0.005), and their number was similar to that found in fat from patients with obesity (p = 0.17). Despite adipocyte hypertrophy and inflammation, lack of the healthy marker perilipin-1 and the presence of crown-like structures were only rarely seen, while they were quite frequent in patients with obesity. CONCLUSIONS: Our data support the idea that cell alterations happen in the early stages of adipocyte development (endothelium/pericyte) in the adipose organ of women affected by lipedema.