<p>Multiple myeloma is one of the most common hematologic diseases. Early detection of the disease and rapid initiation of effective systemic therapy are crucial to prevent permanent physical impairment. The diagnosis should always include a&#xa0;detailed medical history and physical examination, various laboratory chemical parameters, bone marrow puncture, and skeletal imaging. The history and physical examination should serve to detect and prevent developing emergencies and should therefore look for possible signs of impending fractures and neurological deficits. Incipient or manifest renal dysfunction also requires clarification as soon as possible. Laboratory tests with the detection of monoclonal protein are essential for confirming the diagnosis, while routine diagnostics, in particular determination of serum calcium and kidney function, provide indications of the urgency of initiating treatment. Skeletal imaging in the form of a&#xa0;whole-body CT scan is essential for identifying osteolysis and assessing the risk of fracture. Whole-body MRI or positron-emission tomography (PET)-CT can help to distinguish myeloma requiring treatment from precursors. Bone marrow aspirates and biopsies allow the diagnosis to be confirmed in situ, and cytogenetic analyses and modern molecular methods such as next-generation sequencing (NGS) are playing an increasingly important role in diagnosis and prognosis assessment. These techniques help to improve individual risk stratification and optimize therapeutic approaches. Interdisciplinary collaboration in the diagnostic workup is of great importance in order to ensure the best possible care for patients.</p>