Interphase fluorescence in situ hybridization (FISH) is an alternative to conventional chromosome analysis of chronic lymphocytic leukemia (CLL) cells. We analyzed 172 samples from 136 possible CLL cases using a FISH panel. Reflex testing with probes to CCND1, BCL2, BCL3, BCL11A, c-MYC, MALT1, and a break-apart immunoglobulin heavy chain (IGH) probe was done if more than 2 signals for 14q32 occurred. For 111 cases, there were sufficient data for analysis. Of 111 cases, 81 (72.9%) had 1 or more genetic abnormalities. The most frequent abnormality was 13q-, followed by trisomy 12, 11q-, and 17p-. In 13 cases, there were IGH abnormalities. Two cases with CCND1/IGH fusion were reclassified as mantle cell lymphoma. Four CLL cases had IGH fusion with BCL2, BCL3 (2 cases), and BCL11A; no fusion partner was detected in 7 cases. Morphologic features were atypical for CLL in 2 cases with IGH fusion (BCL11A and BCL3). The FISH CLL panel is useful to identify prognostic aberrations and to clarify diagnosis in cases with unusual morphologic features.