Genetic abnormalities are found in 50% of cases of chronic lymphocytic leukaemia (CLL) by cytogenetic analysis and in a higher percentage of patients using molecular techniques. The commonest cytogenetic abnormalities are trisomy 12 and deletions or translocations of the long arm of chromosome 13 usually involving band q14. The genetic consequences of trisomy 12 are unknown but structural abnormalities of chromosome 13q14 frequently involve hetero or homozygous loss of a region distal to the retinoblastoma gene which may be the site of a tumour suppressor gene. Trisomy 12 or loss of one copy of the retinoblastoma gene have been detected by fluorescent in situ hybridisation (FISH) in interphase cells of patients with a normal karyotype. By combining FISH with immunophenotyping, it has been found that trisomy 12 occurs in only 30 to 40% of the malignant clone, suggesting that it is a secondary event in leukaemogenesis. Trisomy 12 is strongly associated with atypical lymphocyte morphology in patients with otherwise typical CLL. Complex karyotypic abnormalities, a high percentage of abnormal metaphases and trisomy 12 but not structural abnormalities of chromosome 13 are associated with a poor prognosis at all stages of the disease. Mutations or deletions of the P53 gene are found in 10 to 15% of patients with advanced CLL and correlate with resistance to treatment and poor survival.