BACKGROUND: Keloid lesions are characterized by mesenchymal cell proliferation and excessive extracellular matrix deposition. Previous microarray analyses have been performed to investigate the mechanism of keloid development. However, the molecular pathology that contributes to keloid development remains obscure. OBJECTIVE: Exploring the underlying essential molecules of keloids using microarrays. METHODS: We performed microarray analyses of keloid and non-lesional skin tissues both in vivo and in vitro. Gene expression levels were compared between tissues and cells. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunopathological staining were used to determine the expression levels of molecules of interest in keloid tissues. RESULTS: Several common molecules were upregulated in both keloid tissues and keloid-lesional fibroblasts. PTPRD and NTM were upregulated both in vivo and in vitro. MDFI and ITGA4 were located at the center of the gene co-expression network analysis using keloid tissuess. qRT-PCR revealed significant expression levels of PTPRD and MDFI in keloid tissues. Immunopathological staining revealed that MDFI-positive cells, which have fibroblast characteristics, were located in the keloid-associated lymphoid tissue (KALT) portion of the keloid tissue. CONCLUSIONS: Our gene expression profiles of keloids distinguished the difference between lesional tissue and cultured lesional fibroblasts, and MDFI was commonly expressed in both tissues and cells. Thus, MDFI-positive cells, which were located in the KALT, might be used in in vitro keloid studies and may play an important role in keloid pathogenesis.