Background: Spinal calcium pyrophosphate deposition disease (CPPD) is uncommon, and often resembles more common spine pathologies causing pain and neural compression. Here, we present two unusual cases of CPPD of the cervical and thoracolumbar spines. Case description: Case 1: A 71-year old female smoker presented with a large epidural mass causing rapidly progressive cervical myelopathy with weakness in the upper and lower extremities. Case 2: A 66-year-old morbidly obese male presented with chronic back pain for several years associated with progressively worsening radicular pain in his left lower extremity. Outcome: The first case is an example of tumoral CPPD involving the facet joint and expanding into the epidural space. The second case was an example of CPPD involving a thoracolumbar facet cyst, resulting in unilateral radiculopathy. Both patients were treated surgically and had significant improvement in symptoms post-operatively. Conclusions: CPPD in the spine is an uncommon diagnosis but should be considered in the differential diagnosis of patients presenting with back pain and associated neurological symptoms. Accurate diagnosis of spinal CPPD is important in that it will guide postoperative management with anti-inflammatory medications and reduce risk of recurrence.