Automated registration of compounds from external sources is necessitated by the numerous compound acquisitions from vendors and by the increasing number of collaborations with external partners. A prerequisite for automating compound registration is a robust module for determining the structural novelty of the input structures. Any such tool needs to be able to take uncertainty about stereochemistry into account and to identify tautomeric forms of the same compound. It also needs to validate structures for potential mistakes in connectivity and stereochemistry. Genentech has implemented a Structure Normalization Module based on toolkits offered by OpenEye Scientific Software. The module is incorporated in a graphical application for single compound registration and in scripts for bulk registration. It is also used for checking compounds submitted by our collaborators via partner-specific Internet sites. The Genentech Structure Normalization Module employs the widely used V2000 molfile format to accommodate structures received from a wide variety of sources. To determine how much information is known about the stereochemistry of each compound, the module requires a separate stereochemical assignment. A structural uniqueness check is performed by comparing the canonical SMILES of a standard tautomer. This paper offers a discussion of the steps taken to validate the chemical structure and generate the canonical SMILES of the standard tautomer. It also describes the integration of the validation module in compound registration pathways.