Multiple myeloma (MM) is a diverse clonal plasma cell malignancy with resultant organ
damage including renal and bone marrow effects, as well as neurologic and immune dysfunction. MM is characterized as clinically and pathologically heterogeneous with significant variability in treatment response and survival. The genetically high-risk myeloma is often manifested as clinical relapsed and refractory disease. In this article, we summarize the most recent progress of molecular diagnosis and targeted treatment of multiple myeloma. We review the landscape of chromosomal abnormalities in myeloma and discuss the clinical impact on patient outcomes. We also present case report of a rare myeloma complication: central nervous system (CNS) myelomatosis. This study will help to understand the biology of CNS myeloma and its therapeutic implications in the era of precision medicine.