The methanol extract of the aerial parts ofMarrubium thessalumBoiss. & Heldr. (Lamiaceae) afforded 30 phenolic metabolites, belonging to the classes of phenylethanoid glycosides, flavonoids and simple phenolic compounds. The crude methanol extract as well as the secondary metabolites were screened for their cytotoxic/cytostatic effects against four human cancer cell lines, specifically HeLa, MCF-7, FM3 and HCT-116 and demonstrated considerable cell growth-inhibitory activity. The differential cytotoxicity of the compounds implied possible structure-activity relationships. Selected compounds were evaluated for their toxicity against human peripheral blood mononuclear cells, where some of them showed marginal toxic effects. The results suggest thatM. thessalumproduces secondary metabolites that demonstrate selective anticancer activity concomitantly with reduced toxicity on lymphocytes. The structure of such compounds can eventually lead to the development of novel pharmaceutical agents. Copyright © 2012 John Wiley & Sons, Ltd.