Isolation of organic molecules directly from Paleozoic to Cenozoic fossils has been documented, which raises important, new questions about the conditions of preservation and the range of paleobiological issues that can be addressed with these new data. Herein, molecules are isolated from fossil echinoderms exceeding 445 Ma in age. Previously, morphological data have been insufficient to establish a consensus regarding early echinoderm evolution. Thus, organic molecules extracted from fossil echinoderm specimens (mostly Paleozoic) belonging to the classes Asteroidea, Blastoidea, Crinoidea, Diploporita, Echinoidea, and Edrioasteroidea are used to assess the position of crinoids and blastozoans within competing echinoderm phylogenetic hypotheses. Fluorescence excitation-emission spectroscopy of organic molecules in fossil extracts are used to compare relationships among hypotheses. These new data support the hypothesis that living eleutherozoans diverged early from stemmed echinoderms, crinoids are nested within the clade that includes other blastozoans, and edrioasteroids are a distinct clade.