This article reviews the most relevant techniques currently used for the evaluation of patients with multiple myeloma. Although bone marrow morphologic examination and electrophoretic analysis of the monoclonal paraprotein and conventional x-rays remain the "gold standard" techniques for fast, accurate, and cost-effective diagnosis, other assays such as molecular cytogenetics, immunophenotyping, MRI, and PET-CT may contribute to a better assessment of patients with myeloma. Here, we will discuss not only the contribution of each technique to differential diagnosis of monoclonal gammopathies, but also the value of each parameter for determining prognosis and for monitoring treatment efficacy. In addition, possible technical pitfalls inherent to each technique will be analyzed.