Fractionation of the EtOH extract of the marine sponge Discodermia calyx led to the isolation of dephosphonocalyculin A (2). The gross structure 2 was deduced on the basis of spactral data. The structure including the absolute stereochemistry has been confirmed by chemical transformation of 2 and calyculin A to a common compound. Dephosphonocalyculin A inhibits protein phosphatases 1 and 2A with IC5o values of 3.0 and 8.2 nM, respectively.