A new tris-guanidine alkaloid, KB343 (1), was isolated from the aqueous extract of a Palauan zoantharian, Epizoanthus illoricatus. The structure of 1 was determined on the basis of spectral analyses of 1 and its derivatives. The absolute configuration for 1 was determined upon comparison of the CD spectrum of 1 to those obtained from density functional theory calculations. The structure of 1 is highly unusual, as three guanidine groups are present in one ring system.