A thorough diagnostic examination is essential before providing endodontic treatment. The sequence of diagnostic procedures must begin with a well-organized review of the medical history. In the early screening process, a health history that reveals a systemic disorder must be investigated further because it may have a significant impact on the dental diagnosis and ultimate endodontic treatment. There are a number of systemic diseases that can cause bone lesions throughout the body. Chronic renal failure is one disorder that may stimulate a secondary hyperparathyroidism that can cause a variety of bone lesions. In some instances these lesions appear in the periapical region of teeth and can lead to a misdiagnosis of a lesion of endodontic origin. The following case report of a patient referred for endodontic treatment demonstrates the importance of understanding the effects of end-stage renal disease on the dental structures.