CD38 expression and chromosomal abnormalities are novel prognostic factors in chronic lymphocytic leukaemia (CLL). However, their value remains undetermined. CD38 was evaluated in 123 patients and chromosomal aberrations in 111 cases with fluorescence in situ hybridization (FISH). CD38 expression was found in 27% of the cases. In addition, seven out of 32 CD38- patients became CD38+ during evolution of the disease. Chromosomal abnormalities included isolated 13q deletion (40%), 12q trisomy (14%), 11q deletion (without 17p deletion) (14%) and 17p deletion (7%). CD38 expression was significantly associated with Binet stages B and C, atypical morphology and 11q deletion. On univariate analysis of survival estimates, advanced Binet stages, CD38+ phenotype, atypical morphology and 11q or 17p deletions were associated with shorter event-free survival (EFS), treatment-free interval (TFI) and overall survival (OS). Multivariate analysis identified both Binet stages and CD38 as independent prognostic factors with regard to EFS and TFI. However, CD38 appeared as an independent factor for OS when restricted to Binet stage A. Chromosomal aberrations were re-evaluated during evolution in 31 cases. The 17p deletion was the most frequent new chromosomal abnormality (35%) and significantly associated with death (64%). In conclusion, CD38 expression and secondary 17p deletion are important poor prognostic indicators, especially in Binet stage A CLL.