Many parameters must be addressed for endodontic therapy to succeed. Because conservation of tooth structure is vital, the pulp chamber and root canal orifices should be located by using a method that is consistent yet accurate. The correlation of occlusal anatomy with the locations of the root canal orifice may aid dentists with access design. This study sought to determine if a correlation existed between occlusal surface anatomy, pulp chamber location, and root canal orifice location. This in vitro study utilized 21 human mandibular first molars. For each specimen, amalgam restorations were placed in the respective cusp tips, with gutta-percha placed in each canal at the level of the furcation. The authors made digital radiographs and occlusal photographs of each complete specimen. The samples were sectioned horizontally at the level of the cementoenamel junction (CEJ). Using a digital software program, the radiographs were superimposed with the digital photographs and correlations of pulp chamber to locate the canal orifice and occlusal surface anatomy. The authors found that the pulp chamber of the mandibular first molar lies more lingual at the level of the CEJ. In addition, the orifices were consistent in their location relative to cusp tip anatomy, a discovery that may assist dentists with the access design.