Current molecular testing workflow and EuroClonality-NDC workflow for LPDs. Genetic alterations required to be tested (green box) can be performed using multiple molecular testing strategies with recognized limitations (orange boxes). The EuroClonality-NDC panel design includes probes to capture all variable (V), diversity (D), and joining (J) genes for all functional immunoglobulin (IG)/TCR loci (blue box) alongside probes designed to cover either the entire coding sequence or specific hotspots in selected exons for 72 genes, probes designed to capture CNAs in clinically relevant genes, and immunoglobulin heavy chain (IGH) switch regions to detect translocations originating from aberrant class switch recombination. A brief summary of the EuroClonality-NDC multisite validation is detailed (yellow boxes). del(13q) was excluded from the final sensitivity and specificity calculations, because the EuroClonality-NDC design only examined the RB1 gene, which resides outside of the minimally deleted region for del(13q).*In addition to the 280 clinical validation samples, an extra 128 samples were included (50 LPD samples with southern blot [SB] data, 39 chronic lymphocytic leukemia [CLL] samples with extensive FISH analysis for CNA validation, 21 reactive lesions, 14 LPD cell lines, and 4 Horizon cell line blends) to aid in assessing EuroClonality-NDC performance. FFPE, formalin-fixed paraffin-embedded; gDNA, genomic DNA; HMW, high molecular weight.