Deletion 13q14 on fluorescence in situ hybridization (FISH) analysis is the most common cytogenetic abnormality in chronic lymphocytic leukaemia (CLL), and is a favourable prognostic biomarker when detected as a sole abnormality. We intensively interrogated clinical outcome in 323 consecutive, untreated CLL patients with isolated 13q- identified within 2 years of diagnosis. We also analyzed outcome in 217 additional patients with deletion 11q22.3 or 17p13.1, or trisomy 12, based on whether these occurred in isolation or in conjunction with 13q-. Patients with a heterozygous 13q- and those with a homozygous deletion had similar time to first treatment (TFT) and overall survival (OS). In contrast, a higher percentage of 13q- nuclei was associated with significantly shorter TFT (P < 0·001). The 5-year untreated rate was 79% for patients with isolated 13q- in ≤65·5% of nuclei compared to 38% among those with 13q- in >65·5% of nuclei (P < 0·001). The percentage of nuclei exhibiting 13q- remained an independent predictor of TFT after controlling for ZAP-70, IGHV, or CD38 (all P < 0·001). Among patients with 13q- plus one other FISH abnormality, concomitant 13q- appeared to attenuate the shorter survival associated with 17p- (P = 0·019). The clinical implications of 13q- in CLL appear more complex than originally appreciated.