In order to evaluate the expression of bone morphogenetic protein 4 (BMP-4) and its intracellular mediator SMAD4 in oral cancer, a study was performed on 91 oral squamous cell carcinoma (SCC) and 21 metastatic lymph node archival specimens. Nine specimens of benign oral mucosa lesions were included as controls. Immunohistochemistry was performed with polyclonal anti-human BMP-4 and monoclonal anti-human SMAD4 antibodies. All specimens of SCC and metastatic lymph nodes showed positive BMP-4 staining, which appeared weak and inconsistent for the control group. The expression was more extended in tumours with perivascular invasion at a statistically significant level. The staining intensity was higher for the metastatic compared to the primary sites. Smad4 was mainly absent in most of the primary and metastatic sites, but was expressed in the control group. Positive BMP-4 expression was associated to negative Smad4 expression at a statistically significant level. The results of the present study indicate that BMP-4 expression varies between SCC tumours with different histopathological traits. Expression of BMP-4 was associated with more aggressive biological behaviour of the tumour. BMP-4 expression did not correspond to Smad4 expression.