<jats:title>Abstract</jats:title><jats:p>Glycolipid analysis of the Caribbean sponge <jats:italic>Amphimedon compressa</jats:italic> has shown it to contain two novel glycosphingolipids, amphiceramide A (<jats:bold>1a</jats:bold>) and B (<jats:bold>2a</jats:bold>), which possess an unusual Δ<jats:sup>6</jats:sup>‐phytosphingosine. The saccharide chain of amphiceramide A is composed of a β‐glucose residue glycosylated at the 6‐position by an <jats:italic>N</jats:italic>‐acetyl‐β‐glucosamine and has never been found before in a natural product. The saccharide chain of amphiceramide B consists of an allolactose [Gal(1β→6)Glc] residue β‐linked to the ceramide and is found here for the first time in a natural glycosphingolipid. In addition, the sponge contains a new molecular species, acetamidoglucosyl ceramide (<jats:bold>3a</jats:bold>), and the known glucosyl ceramide <jats:bold>4a</jats:bold> (halicerebroside A) and melibiosyl ceramide <jats:bold>5a</jats:bold> (amphimelibioside C). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)