The aim of this study was to investigate the contact dependent cellular interactions of neoplastic cells and somatic cells in vitro. These interactions were examined as homotypic and heterotypic interactions with focus on plasma membrane exchange and complete cell fusion of two cells. Plasma membrane exchange between the cancer cells and between cancer cells and primary fibroblasts was characterized in absolute and kinetic terms. It was found that primary human fibroblasts from skin and gingival origin were superior to cancer cells in terms of membrane exchange. This important finding demonstrates that membrane exchange similar to trogocytosis is not only a feature of immune and cancer cells as previously thought but has an important significance as cell-cell communication mechanism involved in tissue homeostasis. Complete cell fusion was examined by tagging the cell nucleus with a non-replicating baculovirus expressing chimeric nuclear proteins tagged with green and red fluorescent proteins. Complete cell fusion was not observed with fibroblasts and was only detected with SAOS-2 and MCF-7 cancer cells. It was shown that this resulted in complete nuclear fusion as the double positive cells were syncarions without exception. A large scale comparative profiling of the plasma membrane proteome of the two osteosarcoma cell lines: the good fuser SAOS-2 and the inferior one MG-63 was undertaken. Several proteins with possible involvement in the cell fusion process were identified. GP73 a protein strongly expressed in hepatocytes-derived syncytial giant cells and SED1/MFG-E8, a glycoprotein with role in sperm-egg fusion were found on the surface of SAOS-2 cells. Additionally, the presence of heat-shock proteins HSP-90 and HSP-70 which are molecular chaperons and interact with wide range of proteins were also detected on both SAOS-2 and MG-63 and thus identified as new bio-markers of osteosarcoma.