The wood-rot basidiomycete Ganoderma colossus has been chemically investigated. Comparative analyses of the natural fruiting body, artificially cultivated fruiting bodies, and mycelial cultures resulted in the isolation, in total, of 13 new highly modified lanostanes, ganocolossusins A-H (1-8) and ganodermalactones T-X (9-13), together with 23 known compounds (14-36). There were significant overlaps of the same compounds among the three different states of the fungal materials. Ganocolossusin D (4) displayed the most potent antimalarial activity against Plasmodium falciparum K1 (multi-drug-resistant strain) with an IC value of 2.4 μM, while it was noncytotoxic to Vero cells at 50 μg/mL.