OBJECTIVE AND IMPORTANCE: The clinical, pathological, and imaging findings in a patient with a chondromyxoid fibroma involving the C2 vertebra are reported. Seven cases that involve the cervical spine have previously been reported in the literature; the posterior vertebral body and posterior elements are the most frequently involved. To our knowledge, this is the first reported case of C2 involvement and craniocervical instability. CLINICAL PRESENTATION: A 20-year-old man presented with intermittent neck pain resulting from a fall 4 years earlier. X-rays and magnetic resonance imaging demonstrated a lytic lesion in the body of C2, as well as instability at C1-C2. INTERVENTION: Preoperative transcatheter angiography and embolization were performed. An expansile tumor of the C2 vertebral body was resected via a transoral approach. Because of craniocervical instability, fusion from the occiput to posterior elements of C1 through C4 was performed. CONCLUSION: Chondromyxoid fibroma is a rare benign bone tumor that is uncommonly found in the spine and may mimic other lesions, particularly radiographically. We report the first known involvement of C2 by this tumor in the modern English-language literature. The patient has had excellent clinical and radiographic resolution of the prior instability with no neck pain, instability, or local recurrence.