Hematological malignancies represent a heterogeneous group of blood neoplasias commonly characterized by abnormal production of blood cells (hematopoiesis). These malignancies comprise a set of prevalent yet clinically diverse diseases that can affect any organ system. Because blood components originate in the bone marrow, wherever the bone might be the site of primary or secondary hematologic neoplasm. Even the calvarial localization of hematological malignancies is a rare finding, the variability in imaging appearances and clinical behavior of these diseases make the primary diagnosis and monitoring of clinical progress a challenging deal that the imaging findings may be subtle, leading to missed diagnosis, or may be nonspecific and confused with infection or another benign disease, leading to incorrect diagnosis. The aim of this chapter is to analyze the clinical, radiological, and biological management and prognosis futures of these calvarial hematological malignancies either in their primary or secondary occurrence according to the World Health Organization (WHO) classification. We specifically study the behaviors of lymphoma, leukemia, and multiple myeloma involving the calvarium.