Selective estrogen receptor modulators (SERMs) significantly affect survival and invasiveness of rodent pituitary adenoma (PA) cells. The impact of three clinically relevant SERMs (bazedoxifene, clomiphene, raloxifene) on invasiveness and on gene and protein expression of invasion-related proteases [matrix metalloproteinase-14 (MMP-14) and A disintegrin and metalloproteinase-12 (ADAM12)] was analyzed in murine PA cells (AtT-20 and TtT/GF). All SERMs significantly decreased cell invasiveness. Moreover, SERMs significantly decreased expression of ADAM12 mRNA in both cell lines and of MMP-14 mRNA in TtT/GF cells. Invasion rates of AtT-20 and TtT/GF significantly decreased after ADAM12 gene silencing, and the invasion rate of TtT/GF cells significantly decreased after MMP-14 gene silencing. All SERMs affected ADAM12 protein expression in AtT-20 cells whereas bazedoxifene and raloxifene decreased MMP-14 protein expression in TtT/GF cells. We conclude that SERMs attenuate invasiveness of murine PA cells by downregulating expression levels of invasion-related proteases MMP-14 and ADAM12.