Protein tyrosine phosphatases (PTPases) balance the action of tyrosine kinases to maintain a set level of cellular tyrosine phosphorylation. Increases in tyrosine phosphorylation produced by transformation with constitutively active tyrosine kinases can initiate cellular proliferation. PTPases may act as tumor suppressors to counteract the transforming potential of oncogenic kinases. However, recent evidence suggests that PTPases have the potential to act as positive mediators of mitogenic signaling. If PTPases are acting as tumor suppressors, the expression of an inactive PTPase may cause an increase in overall tyrosine phosphorylation of cellular proteins, resulting in cellular transformation. Alternatively, overexpression of PTPases that play a positive role in signal transduction might also lead to proliferation. The role that each PTPase plays may depend in the cellular context in which it is expressed.