The diagnosis of chronic lymphocytic leukaemia (CLL) is based on clinical and laboratory features. Morphology and immunophenotype are the key initial diagnostic tests. In cases with atypical features, these investigations should be complemented with cytogenetics and/or histology to confirm the diagnosis and to exclude other B-cell disorders. Morphologically, CLL can be classified into typical and atypical forms. Cell-marker studies provide a robust foundation to establish the diagnosis as the lymphocytes have a distinct immunophenotypic signature. Although no single antigen is exclusively expressed in CLL cells, when several markers are compounded into a scoring system the results allow firming up of the diagnosis. Other immunological markers, such as CD38 or ZAP-70, have an important prognostic impact. Fluorescence in-situ hybridization (FISH) analysis also provides prognostic information, chiefly by detecting 17 (p53 locus) and 11q deletion, and may determine the type of therapy.