Within Mollusca, cephalopods exhibit a particularly complex nervous system. The adult brain is formed from the fusion of several “typical” molluscan ganglia but it remains poorly understood how these ganglia emerge, migrate, and differentiate during embryogenesis. We studied the development of both central and peripheral nervous system by antibodies raised against α-tubulin and tyrosine hydroxylase (TH) in Sepia officinalis embryos to visualize neurites and catecholamine-containing neurons, respectively. In early embryos, when organs start delineating, some ganglia already exhibited a significant fiber network. TH-like immunoreactivity was detected in these fibers and in some primary sensory neurons in the embryo periphery. These data attest to the occurrence of an early embryonic sensory nervous system, likely effective, transient in part, and in relation to the perception of external cues. Concerning the peripheral nervous network, the stellate ganglia emerged as a plexus of numerous converging axons from TH-like immunoreactive sensory cells, first at the mantle edge, and then in the whole mantle surface. Later, TH-immunopositive motor fibers, originating from the stellate ganglia, penetrated the circular muscles of the mantle. These patterns reveal the setup of a mantle midline with likely attractive and repulsive properties. Our findings seem to challenge the widespread, still accepted, view of a late differentiation of cephalopod ganglia, and provides significant data for further investigations about axonal guidance during cephalopod development. J. Comp. Neurol. 517:539–549, 2009. © 2009 Wiley-Liss, Inc.