Ryanodine receptors (RyRs) have been previously implicated in the proliferation of human T-lymphocytes and melanocytes as well as in the motility of astrocytes. We have examined RyR expression in 57 ductal, human breast cancer specimens, by immunohistochemistry. Moderate to high RyR immunostaining was found in 47 (82%) of the specimens. There was a direct correlation between RyR levels and tumor grade (r = 0.48, p = 0.0002). We have also examined the effect of the RyR agonist 4-chloro-m-cresol on the in-vitro growth of two human breast cancer cell lines, MCF-7 and MDA-MB-231. Treatment with 4-chloro-m-cresol inhibited the growth of both breast cancer cell lines, in a dose-dependent manner, with half-maximal inhibition observed at 30 to 50 microg/mL (210-351 microM). Our data suggest that RyR could serve as prognostic indicator and/or as a target for breast cancer treatment.