Objective: The purpose of this case report is to describe a case where calcium pyrophosphate dehydrate crystal deposition disease (CPPD) simulated osteoarthritis of the knee. Clinical Features: A 78-year-old woman had a 2-week history of severe right knee pain accompanied by mild swelling. The onset was sudden and did not involve a history of trauma or previous injury to the right knee. Inspection and palpation revealed pain along the medial joint line and marked difficulty ambulating. Results of Lachman's test, anterior drawer test, and posterior sag sign were negative upon orthopedic assessment. Diagnostic imaging was performed and showed degenerative changes with diffuse calcification of the fibrocartilage and hyaline articular cartilage within the knee joint and the medial collateral ligament consistent with the appearance of CPPD crystal deposition. Intervention and Outcome: Low-level laser therapy was performed to the affected medial joint line of the knee, and knee stabilization exercises were given. Lower Extremity Function Scale changed from 34% to 60% after 4 weeks of care. Conclusion: Although knee osteoarthritis is much more common than knee CPPD, it is important to consider both diagnoses in elderly patients who present with unilateral knee pain. Diagnosis should be based on clinical presentation, history, and radiographic or histological means to ensure accuracy and proper diagnosis. (J Chiropr Med 2016;15:219-223)