The aim of this work was to examine the chemical composition and antiproliferative activity of Salvia leriifolia Benth. and Salvia acetabulosa L. oils. S. leriifolia oil was characterized by 50 components, whereas 19 components were identified in S. acetabulosa. S. leriifolia oil was characterized by camphor (10.5%), 1,8-cineole (8.6%), camphene (6.2%), and alpha-pinene (4.7%). alpha-Pinene (52.3%), 1,8-cineole (27.7%), and camphor (6.7%) were the major components in S. acetabulosa oil. Both oils exerted a strong antiproliferative activity comparing with vinblastine against COR-L23 with 50% inhibitory concentration (IC(50)) values of 7.5 and 6.5 microg/mL for S. leriifolia and S. acetabulosa, respectively. Salvia oils showed an interesting activity also on C32 (IC(50) = 6.3 and 9.1 microg/mL for S. acetabulosa and S. leriifolia, respectively). S. acetabulosa was also found to possess cytotoxic activity against renal adenocarcinoma (IC(50) = 6.8 microg/mL). The results clearly showed that for both Salvia species the antiproliferative activity could not be related to the major abundant compounds. Consequently, the minor components may be involved in some type of synergism with the other active compounds.