Four new lanostane triterpenes, colossolactone V (1), colossolactone VI (2), colossolactone VII (3), and colossolactone VIII (4), were isolated from the fruiting bodies of the Vietnamese mushroom Ganoderma colossum, together with the known compound colossolactone E (5). The structures of 1- 4 were assigned on the basis of spectroscopic evidence, and their absolute configurations were determined by CD spectroscopy and the Mosher ester method. Compounds 1- 5, as well as two previously isolated compounds [schisanlactone A (6) and colossolactone G (7)] from the same mushroom, were evaluated for inhibition of HIV-1 protease, with IC 50 values for the most potent compounds ranging from 5 to 13 microg/mL.