In oral and maxillofacial surgery, epinephrine is routinely used for cancer resection and it is important to clarify the effects of this agent on cancer. We found here that the clinically relevant concentrations of epinephrine (10, 50 and 100 microg/ml) decreased the invasion ability of oral squamous carcinoma (Sa3) cells. In the Sa3 cells treated with epinephrine (10, 50 and 100 microg/ml), migration, morphological changes and formation of actin stress fibers were inhibited and intracellular cyclic adenosine monophosphate (cAMP) increased significantly. These findings suggest that epinephrine inhibits the invasion of cancer cells by modulating intracellular cAMP and that clinicians could use epinephrine effectively for the surgical resection of the cancer.