PC3 cell line contains different cell variants. A first variant grows as spherical multicellular aggregates and shows anchorage-independent growth. A second variant grows as single small rounds and shows anchorage-dependent growth without cell spreading. A third variant, representing the most abundant population, grows as adherent cells. These populations differ in alpha 2 beta 1 and alpha 3 beta 1 integrin expression with low levels in the suspended (S) cells, intermediate in partially adherent (R) cells and high in adherent cells (A). TPA, which up-regulates the expression of beta 1 integrins, increases invasiveness of cells. In addition, PC3 variants differ in MMP9 and uPA secretion and activity. High levels of TIMP1 and PAI1 present in S variant reduce MMP9 and uPA activities, respectively. In conclusion, PC3 cell line shows variants with strong phenotypic heterogeneity reflecting also the in vitro culture condition. Our observations may explain some of the contradictions in the literature. Therefore, the data obtained with this line should be evaluated more carefully, considering morphological and functional characteristics of the possible variants in the cell population. However, this heterogeneity may represent a good model in the study of tumor progression.