Dupuytren's disease (DD) is a benign fibroproliferative tumor with an unknown etiology and high recurrence postsurgery. Several observations suggest the possible involvement of skin overlying nodule (SON) and the subcutaneous fat in the pathogenesis of DD. This study aims to (1) compare the gene expression levels of SON and subcutaneous fat in DD and normal subjects and (2) to compare transverse palmar fascia (Skoog's fibers) from DD patients as internal control tissue, with palmar fascia (transverse carpal ligament) from patients undergoing carpal tunnel release as external control. Skin, fat, and fascia were obtained from five DD patients of Caucasian origin (age = 66 +/- 14) and from five control subjects (age = 57 +/- 19) undergoing carpal tunnel release. Total ribonucleic acids was extracted from each sample and used for complementary deoxyribonucleic acid synthesis. Real-time quantitative polymerase chain reaction was used to assess the gene expression levels of six candidate genes: A disintegrin and metalloproteinase domain (ADAM12), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), iroquois homeoboxprotein 6 (IRX6), periostin, osteoblast specific factor, proteoglycan 4, and tenascin C. Using independent t test, ADAM12, ALDH1A1, and IRX6 expression levels in DD fats were significantly (p < 0.05) higher than those in the controls. There is no significant difference in the gene expression levels of all six genes when comparing disease and control fascia and skin. Interestingly, ADAM12 up-regulation has also been observed in several other fibrotic and proliferative disorders. In conclusion, this study demonstrates potential roles for subcutaneous fat in DD pathogenesis as well as supports the use of transverse palmar fascia as appropriate control tissues in DD research.