This study aimed to identify new biomarkers for metal exposure in two bivalve species. Suppressive Subtractive Hybridization (SSH) was employed to evaluate the transcriptomic response of Cerastoderma edule and Ruditapes philippinarum to metal pollution. Protein synthesis and catalytic activity were the most affected metabolic processes in C. edule and R. philippinarum, respectively. Also, different genes responded to the effect of contamination in each species. The different response observed in both species reinforces the importance of including more than one bioindicator species in risk assessment studies. These results provide the basis for new studies, which are necessary for further validation of the use of the identified genes as molecular biomarkers for metal exposure.