The aim of this study is to determine the chemical composition, and evaluate the genotoxic, and anti-growth potency of the methanol extracts of lichen species Hypogymnia physodes (L.) Nyl. (HPE). Anti-growth effect was tested in two different human breast cancer cell lines (MCF-7 and MDA-MB-231) by the MTT and ATP viability assays and apoptosis was assayed by the caspase-cleaved cytokeratin 18 (M30-antigen). Genotoxic activity of HPE was studied using chromosome aberration and micronuclei tests in human lymphocytes culture in vitro. The chemical composition of H. physodes was analyzed by using direct thermal desorption method coupled with comprehensive gas chromatography–time of flight mass spectrometry (GCXGC-TOF/MS). Our results indicate that HPE has an anti-growth effect at relatively lower concentrations, while relatively higher concentrations are required for genotoxic activity. HPE, therefore, seems to represent a therapeutic potential and poses new challenges for medicinal chemistry. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 804–813, 2014.