The definitive demonstration of the clonal origin of an expanded B or T cell population is achieved by the molecular analysis of B or T cell receptor gene rearrangement. However, in recent years techniques that are both sensitive and relatively easy to carry out have been introduced as the first step to the diagnosis of clonality. These include immunochemical analysis of serum and urine to characterize their monoclonal immunoglobulin components, and immunophenotypic studies of peripheral blood or tissue cells. The most widely used techniques are reviewed here, with particular emphasis on the clinical applications of immunofixation electrophoresis and multiparametric cytofluorimetric procedures.