Seven plasma cell lines from patients with smoldering (group A) and overt myeloma (group B) were investigated for both phenotypic markers and in-vitro properties, including sensitivity to apoptosis, cytotoxicity, cell adhesion, chemotaxis and bone interaction. Cell lines from group A underwent apoptosis whereas those from group B were apparently resistant, promoted cytotoxicity in target cells and enhanced both adhesion and migratory functions upon appropriate activators. In addition, MCC-2, a group B cell line from a patient with severe osteolytic disease of the skeleton produced erosive lacunae on bone substrates, whereas this effect was almost absent with cell lines from group A. Concurrent deregulation of relative markers, in combination with peculiar properties including resistance to apoptosis and high cytotoxic potential, as well as adhesion, chemotaxis and bone pathophysiology interactions, may thus identify myeloma cells with aggressive phenotype driving these biological activities in vitro and perhaps in vivo.