Lymphoplasmacytic lymphoma (LPL) is a B-cell lymphoproliferative disorder typically involving the bone marrow with infiltration by small lymphocytes and plasma cells. Studies have identified MYD88 L265P mutation as a diagnostic marker to distinguish LPL from other small B-cell lymphomas. Detection rates for this mutation have varied depending on the analytic methodology, with previous data suggesting that routine next-generation sequencing (NGS) does not demonstrate the required sensitivity to reliably detect MYD88 L265P. NGS has become part of routine clinical testing because it allows detection of variants across multiple genes. To study the utility of NGS in the detection of MYD88 L265P, we performed droplet digital PCR (ddPCR) and routine NGS on a cohort of 34 cases of lymphoid neoplasms (22 LPL, 4 CLL, 1 MCL, 1 MGUS, 2 plasma cell myeloma, and 4 negative bone marrow cases). We utilized manual review and BAMtools to assess MYD88 L265P in NGS cases. Limit of detection for ddPCR was determined to be 0.4 % variant allele frequency (VAF) with 10 ng DNA input. MYD88 L265P VAF detection by NGS and ddPCR was comparable down to 0.5 % VAF (R