Atraumatic vertebral compression fractures are a common clinical problem, especially in elderly population. Metastases are the most frequent source of bone tumors, and the spine is a common site of metastatic disease; in case of cortical involvement or osteolysis, they may result in pathological compression fractures. Atraumatic compression fractures may result from other primary neoplasms of vertebrae and also from osteomyelitis, Paget's disease, hyperparathyroidism and other metabolic processes. Osteoporosis is a common source of vertebral compression fractures in elderly population, which may be indistinguishable from those of metastatic origin. The differentiation between osteoporotic compression fractures and malignant fracture is necessary to establish an appropriate staging and a therapeutic planning, especially in the acute and subacute stages. Anamnestic data about preexisting disease can be useful to individuate the potential cause of vertebral collapse. Plain radiography shows some difficulties in distinguishing whether the fracture represents a consequence of osteoporosis, a metastatic lesion or some other primary bone neoplasm. Computed tomography is one of the most suitable imaging techniques for the evaluation of bone structure and fragments and to establish the degree of cortical bone destruction; MR imaging (MRI) is the most helpful radiological investigation in order to provide the basis for the distinction between metastatic and acute osteoporotic compression fractures. The most relevant MRI findings to establish a differential diagnosis are described.