OBJECTIVES AND METHODS: Lichens are an interesting source of potential anti-tumor compounds, among which usnic acid and atranorin seem to be the most promising, but their impact on invasive potential of tumor cells has not yet been comprehensively addressed. The aim of the study was focused on the impact of the two lichen metabolites, on the viability (by Trypan blue test and fluoresceine diacetate and ethidium bromide assay), proliferation (cell counting in a Burker's chamber), apoptosis (flow cytometry analysis and Western blot) and motile activity (cell movement recording and image analysis) and actin cytoskeleton organization (immunofluorescent staining) of melanoma HTB-140, prostate cancers DU-145 and PC-3, normal human skin fibroblasts and prostate epithelial PNT2 cells, with special emphasis to their selectivity and versatility. RESULTS: Both compounds exerted strong inhibitory effects on cancer cell proliferation, migration and actin cytoskeleton organization, while their effect on apoptosis process was less relevant. The impact of usnic acid on the examined cancer cells was found more efficient in comparison to atranorin. Also, selective effect of both agents on tumor cells was observed. SIGNIFICANCE: The ability of usnic acid and atranorin to inhibit cancer cells motility may have future implications for development of new therapeutic strategies targeted at the interference with the metastatic cascade. Actins/metabolism, Antineoplastic Agents/*pharmacology, Apoptosis/drug effects, Benzofurans/*pharmacology, Cell Line, Tumor, Cell Movement/drug effects, Cell Proliferation/drug effects, Cell Survival/drug effects, Cells, Cultured, Cytostatic Agents/*pharmacology, Fibroblasts/drug effects, Humans, Hydroxybenzoates/*pharmacology, Male, Melanoma, Prostatic Neoplasms, Actin cytoskeleton, Apoptosis, Atranorin, Cytotoxic, Metastasis, Usnic acid