Peterson JF, Pearce KE, Meyer RG, et al. - Through a retrospective review of the Mayo Clinic cytogenetic database of 470 individuals assessed by fluorescence in situ hybridization (FISH) testing for TP63 rearrangements in formalin-fixed, paraffin-embedded (FFPE) tissue using both breakapart (BAP) and dual-fusion (D-FISH) probes, experts examined their 5-year experience with clinical FISH testing for TP63 rearrangements using both TP63 BAP and TBL1XR1/TP63 D-FISH probes, assessed the regularity of TP63 rearrangements and the distribution of TBL1XR1 vs alternate partner loci, and evaulated whether both probe sets were needed in up-front FISH testing. This was the largest series of TP63 rearrangements till date. Among cases referred to the large reference laboratory for TP63 FISH testing, the frequency of positive outcomes was 5.3%. Nearly half of the TP63 rearrangements have a TBL1XR1 partner. For up-front testing of FFPE tissue samples, TP63 BAP FISH testing is adequate. Nevertheless, due to the genomic proximity of the TP63 and TBL1XR1 loci, reflex TBL1XR1/TP63 D-FISH testing in positive and equivocal cases is suggested.