The detection of chromosomal translocations by fluorescence in situ hybridization (FISH) is widely performed, but very few studies have attempted to apply this technique to paraffin-embedded routine biopsy samples. We report the analysis of paraffin sections from 36 B-cell lymphoma biopsies for MYC translocation breakpoints by FISH. The probes consisted of multi-YAC constructs that flanked the breakpoint region and that, therefore, separate upon a chromosomal translocation and generate split (or "segregated") signals (rather than a more ambiguous "co-localization" pattern, obtained when the two partners in a hybrid gene are detected). The results were assessed by a simple approach that avoids the counting of signal numbers per nucleus and so is appropriate for use in routine practice. A total of 19 of the 36 lymphomas were scored as positive for MYC translocation and this included 16 of the 20 patients in whom classic cytogenetics had shown the presence of the (8;14) translocation (or one of its two variants). We conclude that this two-colour "split-signal" technique based on breakpoint flanking probes can readily detect chromosomal translocations in paraffin sections. Furthermore, our results suggest that cases categorized as "atypical Burkitt's/Burkitt-like" lymphoma (at least for adult patients) are heterogeneous with respect to translocations involving the MYC oncogene, as well as immunophenotype and clinical features.