Proteinase activated receptors (PARs), a small subfamily of G protein-coupled receptors with four members, PAR₁, PAR₂, PAR₃ and PAR₄, are expressed in various tumours from epithelial origin and can play an important role in tumour progression and metastasis. Within the complex intracellular PAR signaling networks triggered by PARs, an elevation in intracellular free calcium ion concentrations represents a key second messenger system. In this review, we summarize current information about the mechanisms whereby PARs can signal via intracellular calcium in the setting of cancer and we discuss possibilities for using the PAR-[Ca(2+)](i) signaling pathway as a target for the therapy of epithelial cancer.