Tumor angiogenesis is influenced by a large number of angiogenic factors among which vascular endothelial growth factor (VEGF) is one of the most important cytokines. Together with hepatocyte growth factor/scatter factor (HGF/SF), c-Met receptor forms a paracrine signaling system. The aim was to study the characterization of the proteins, VEGF, c-Met and HGF/SF with expression pattern and possible co-expression in secondary pleural tumors. Biopsy specimens of the pleural region from 70 patients were chosen and analyzed using immunohistochemistry and in situ hybridization. In the investigated tumors, a marked intracytoplasmic expression, sometimes over-expression of VEGF, c-Met and HGF/SF was detected. This expression was not connected to certain tumor types or a certain histogenetic origin of the tumor. These results indicate a role of these factors in angiogenesis. The synthesis of VEGF and c-Met within the tumor cells was established by in situ hybridization. There was a significant co-expression of VEGF and c-Met/HGF. Thus, autocrine stimulation of these angio-genetically effective systems may be present here. Importantly, the autocrine mechanism between over-expressed c-Met and HGF/SF in malignant tumors, already preferred by other authors, with demonstration of the proteins in the same tumor cells, has to be assumed in the process of pleural metastatic spread. Simultaneous synthesis of these three different proteins is also possible via the plasminogen-urokinase system. VEGF is reported to increase vascular permeability, which in turn causes pleural effusions. The results presented here may be the basis for possible future palliative therapeutical strategies in malignant pleural effusions.