Conventional cytogenetic data and fluorescence in situ hybridization (FISH) interphase cytogenetic studies have shown that trisomy 12 is found in many cases of B-cell chronic lymphocytic leukemia (B-CLL). Several reports indicate that +12 is an acquired numerical cytogenetic abnormality, and may be associated with a worse prognosis or more extensive disease. Wright-Giemsa-stained blood or bone marrow smears obtained after initial diagnosis, and subsequent lymph node cells, bone marrow aspirate smears, or effusions were retrospectively studied from five patients whose disease underwent morphologic transformation from typical B-CLL to a high grade lymphoproliferative disease (Richter's syndrome). Using an alpha-satellite DNA probe to the centromere of chromosome 12, trisomy 12 was found in a proportion of cells from all five specimens with high grade lymphoproliferative disease, but in only one of five samples collected before transformation. These data suggest that +12 is an acquired cytogenetic abnormality in CLL and has a high frequency in Richter's syndrome. Because only a subpopulation of the neoplastic cells contain an extra copy of chromosome 12, it is unlikely that this numerical abnormality plays a direct role in transformation to high grade lymphoproliferative disease.