The diagnosis of multiple myeloma (MM) can be challenging, especially in patients with light-chain or non-secretory disease. The disease should be excluded in patients presenting with unexplained anaemia or renal failure and suspected in patients with signs of back pain combined with other systemic symptoms, such as fatigue and weight loss, or back pain combined with abnormal blood tests. The diagnosis is based on clinical, biological and radiological abnormalities that are resumed in the current article. At diagnosis, additional cytogenetic testing is important to determine the prognosis and guide physicians in their treatment choices. The disease is generally monitored by quantifying the monoclonal proteins in blood or urine. The follow-up of patients can be further tailored to the patients’ general status, obtained response and disease characteristics.