We analyzed the features of chronic lymphocytic leukemia (CLL) with multiple abnormalities (MA) detected by FISH. A local database including 2095 CLL cases was used and 323 with MA (15.4%) were selected. MA was defined by the presence of two or more alterations (deletions of 13q14 (13q-), 11q22 (11q-), 17p13 (17p-) or trisomy 12 (+12)). The combination of 13q- with 11q- and 13q- with 17p-, accounted for 58.2% of the series, in contrast to 11q- with 17p- (3.7%). Patients carrying MA since diagnosis presented a short time to first therapy (TTFT) (27 months) and overall survival (OS) (76 months). The combinations including 17p- had a shorter OS (58 months) than the ones without 17p- (not reached, p = .002). Patients with a complex-FISH were the ones with worse OS (34 months). MA imply poor prognosis when they emerge at diagnosis, probably due to the high incidence of bad prognosis markers, which may be a reflection of a more complex karyotype.