Aim Multiparametric flow cytometry is an established modality in diagnostic and disease response assessment of plasma cell dyscra-sias. Peter MacCallum Cancer Centre (PMCC) employed 4-colour plasma cell flow cytometry (PCFC) with 0.01% sensitivity, but the increasing clinical demand for consistently high sensitivity precipitated purchase of an 8-colour platform. Solutions to technical challenges during validation are presented. Methods An 8-colour plasma cell (PC) antibody panel was designed from the clinical literature. Seventeen bone marrow aspirate samples were analysed concurrently on FACSCalibur and FACSCanto II instruments. Antibody titration, photomultiplier tube voltage, compensation and control testing were compared. Results The antibody panel was revised due to influence of lysate and poor signal-to-noise ratio from auto-fluorescence of antibodies crucial to the distinction between normal and abnormal PCs (CD19, CD45, CD56). Further refinement included substituting isotype with internal controls and incorporation of additional diagnostic and prognostically relevant antibodies. The final panel demonstrated superior sensitivity, specificity, precision and accuracy to that of the established panel and additional information on the lymphopoietic compartment, of particular interest to our research clinicians. The reporting template has therefore expanded to accommodate malignant and normal PC phenotypes, lymphocyte subsets, and evidence-based interpretive comments. Conclusion 8-colour PCFC has been validated and implemented at PMCC with subsequent improvements in diagnosis, prognostication and MRD detection. Multiparametric flow cytometry is an established modality in diagnostic and disease response assessment of plasma cell dyscra-sias. Peter MacCallum Cancer Centre (PMCC) employed 4-colour plasma cell flow cytometry (PCFC) with 0.01% sensitivity, but the increasing clinical demand for consistently high sensitivity precipitated purchase of an 8-colour platform. Solutions to technical challenges during validation are presented. An 8-colour plasma cell (PC) antibody panel was designed from the clinical literature. Seventeen bone marrow aspirate samples were analysed concurrently on FACSCalibur and FACSCanto II instruments. Antibody titration, photomultiplier tube voltage, compensation and control testing were compared. The antibody panel was revised due to influence of lysate and poor signal-to-noise ratio from auto-fluorescence of antibodies crucial to the distinction between normal and abnormal PCs (CD19, CD45, CD56). Further refinement included substituting isotype with internal controls and incorporation of additional diagnostic and prognostically relevant antibodies. The final panel demonstrated superior sensitivity, specificity, precision and accuracy to that of the established panel and additional information on the lymphopoietic compartment, of particular interest to our research clinicians. The reporting template has therefore expanded to accommodate malignant and normal PC phenotypes, lymphocyte subsets, and evidence-based interpretive comments. 8-colour PCFC has been validated and implemented at PMCC with subsequent improvements in diagnosis, prognostication and MRD detection.