A spiroacetal compound named paecilospirone was isolated from a marine fungus Paecilomyces sp. collected at Yap Island. Paecilospirone was found by the screening assay for detecting inhibitors of microtubule assembly using conidia of Pyricularia oryzae. The structure was assigned based on the spectroscopic data. This is the first report of the isolation and characterization of spiro[chroman-2,1'(3'H)-isobenzofuran] derivative as a natural product.