Chronic lymphocytic leukemia (CLL) follows an extremely variable clinical course with overall survival times ranging from months to decades. The clinical staging systems do not allow one to predict if and at what rate there will be disease progression in an individual patient diagnosed with early stage disease. There has been intensive work on clinical and biological factors of potential prognostic relevance that may add to the classic assessment provided by the staging systems. Among these are: Laboratory parameters reflecting the tumor burden or disease activity such as lymphocyte count, lactate dehydrogenase (LDH) elevation, bone marrow infiltration pattern or lymphocyte doubling time (LDT), serum markers such as soluble CD23, beta2-microglobulin (beta2-MG) or thymidine kinase (TK), and genetic markers of tumor cells such as genomic aberrations, the mutation status of the variable segments of immunoglobulin heavy chain genes (VH), or surrogate markers for these factors (CD38, ZAP-70, LPL). Thirty patients were included in our study, the investigation included CD38 expression, ZAP-70 expression, and interphase Fluorescence In Situ Hybridization (FISH) for the detection of trisomy 12, del 13q14.3, del 17p13, and del 11q22.3. Our results showed positive statistical significant correlation between ZAP-70 expression and CD38 expression with some of the chromosomal aberrations encompassing bad prognosis as ATM and p53. Also CD38 expression was positively correlated with trisomy 12 and p53 deletions. Chromosomal aberrations were found to be present in 76.6% of our patients with 13q deletion as the most frequent abnormality in our patients (46.7%), followed by trisomy 12 (36.7%), then ATM and p53 deletion (26.7%) each. Another interesting finding in our study is the fact that 100% of the ZAP-70 positive patients were of bad prognosis, 58.3% of the CD38 positive cases, 81.8% of the positive trisomy 12 cases, 100% of the ATM deletion, 62.5% of the p53 deletion, and 64.3% of the 13q- cases were also of bad prognosis, which indicates that ZAP-70, trisomy 12, and ATM deletion are powerful indicators of prognosis. We conclude that FISH for the detection of the most important chromosomal aberrations in CLL is an important laboratory parameter that is recommended for assessment and correlation with simultaneous evaluation of ZAP-70 and CD38 expression which could help in the prediction of outcome of CLL patients.