A wide range of pathologic processes may involve the floor of the mouth, the part of the oral cavity that is located beneath the tongue. They include lesions that arise uniquely in this location (eg, ranula, submandibular duct obstruction) as well as various malignancies, inflammatory processes, and vascular abnormalities that may also occur elsewhere in the head and neck. Some lesions that arise in superficial tissues such as the mucosa may be easily diagnosed at physical examination. However, computed tomography, magnetic resonance imaging, or ultrasonography may be necessary for a reliable assessment of lesion extension to deeper structures. In such cases, knowledge of the complex muscular, vascular, glandular, ductal, and neural anatomy of the region is important for accurate diagnosis and treatment planning. Familiarity with the radiologic imaging appearances of the floor of the mouth and recognition of anatomic landmarks such as the mylohyoid and hyoglossus muscles are especially useful for localizing disease within this region.