Several studies have shown that different growth factors are involved in the pathogenesis of palmar fibromatosis. The aim of the present study was to investigate whether transforming growth factor alpha (TGF-alpha) and its cellular receptor, epidermal growth factor receptor (EGF-R), are expressed in palmar fibromatosis. Nodules from 20 patients with palmar fibromatosis and control normal palmar fascias were studied by the reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR followed by Southern blotting demonstrated that palmar fibromatosis nodules contained high levels of TGF-alpha and EGF-R messenger RNA (mRNA) transcripts, while normal fascias showed only low levels. Depending on the degree of cellularity and fibrosis, the three following histological phases were recognized in palmar fibromatosis nodules: proliferative, involutional, and residual. Immunohistochemistry, using alpha-smooth muscle actin as a cellular marker for myofibroblasts, revealed that TGF-alpha and EGF-R are co-expressed by myofibroblasts in the highly cellular areas of both proliferative and involutional phases, while they are absent or only focally detectable in the fibroblasts of normal fascia and in hypocellular and fibrotic areas of both involutional and residual phases. The restricted co-expression of TGF-alpha and EGF-R to myofibroblasts, the proliferating cellular component of nodules, suggests that an autocrine and/or juxtacrine growth stimulation by TGF-alpha via the EGF-R may be involved in the pathogenesis of palmar fibromatosis.