Bioactivity-guided fractionation of the latex of Euphorbia poisonii Pax. (Euphorbiaceae) led to the isolation and characterization of a new tigliane diterpene, 12-deoxyphorbol 13-(9,10-methylene)undecanoate (3), together with five known diterpenes (1, 2, 4−6). When evaluated for cytotoxicity in a panel of six human solid tumor cell lines, the diterpene esters, 1−3, 5, and 6, were selectively cytotoxic for the human kidney carcinoma (A-498) cell line with potencies for 2 and 3exceeding that of adriamycin by ten thousand times. Details of the isolations, structural analyses, and cytotoxic activities are described.