Lymphedema is caused by dysfunctional lymph vessels or as a complication of cancer treatment leading to edema and adipose tissue deposition. One hypothesis is that adipocyte hypertrophy contributes to the volume increase in lymphedema. The aim of the study was to compare adipocyte size in arm and leg lymphedema and controls. The adipocyte size difference was also compared between the arms and legs. Furthermore, any link between adipocyte size difference and gender, lymphedema onset, duration, previous radio- and chemotherapy was studied, as well as any relationship to total excess volume increase in the extremities, body mass index (BMI) and body weight. Adipose tissue biopsies from the lymphedematous and non-affected extremities were taken from 47 patients. The adipocytes sizes were measured using an Olympus PROVIS microscope, Olympus DP50 camera (Olympus, Tokyo, Japan) and ImageJ program (NIH, Bethesda, MD). Additional information was obtained from the Lymphedema Center database. The data were assembled in Excel and statistics was calculated in SPSS Statistics 23 (IBM, Armonk, NY). The adipocyte size (mean ± SEM) in the lymphedematous extremities was significantly larger, 8880 ± 291 μm, compared to the adipocyte size in the non-affected extremities, where it was 7143 ± 280 μm, i.e. 24% larger ( < .001). The adipocyte size increase was larger in arm than in leg lymphedema. No correlation was found between adipocyte size and gender or onset. However, a negative correlation was found between adipocyte size difference and duration. No correlation was found between adipocyte size and previous chemo- or radiotherapy. There was a positive correlation between adipocyte size and BMI. Hypertrophy of adipocytes was seen in the lymphedematous extremities versus control and contributes to the excess volume.