The application of molecular diagnostics to aid transplant phenotypic assessment has not been universally adopted in solid organ transplantation, despite the extensive research performed across the last 2 decades by multiple research groups. Seminal work from Halloran et al has led to the development of the commercially available Molecular Microscope diagnostic system that uses microarray-based mRNA assessment of renal allograft tissue to potentially improve diagnostic precision beyond histology alone, and this commercial system has since been extended to heart and lung transplants. However, the requirement for an extra biopsy core that undergoes processing and molecular assessment at a centralized facility has limited its universal accessibility. A molecular diagnostic panel that uses a decentralized, open-access system, with rapid and ease of access to sample processing and results to allow timely clinical decision making on a global scale, remains elusive. Active efforts have been made in recent years by the Banff Consortium to address these shortfalls. Following its 2017 kidney meeting report that presented a validated, consensus gene list from published studies across various allograft phenotypes,1 the Banff Molecular Diagnostics Working Group created the Banff Human Organ Transplant (B-HOT) gene panel.2 From major gene/transcript publications consisting primarily of microarray data from kidney, heart, lung, and liver allograft biopsies across relevant clinical phenotypes (including rejection, tolerance, drug-induced toxicity, and viral infections), the Molecular Diagnostics Working Group prioritized 670 unique genes, with additional genes considered relevant, to create the final nonproprietary but commercially available 770-gene panel that uses the NanoString platform. The appeal of this technology lies in its requirement only for formalin-fixed, paraffin–embedded (FFPE) tissue as the RNA source that circumvents the need for separate sampling that is needed for microarray assessment and may be a more practical and accessible method of allograft gene/transcript expression assessment. Of relevance, a recent study described that, in transplant biopsy samples split for FFPE and RNAlater, with RNA then extracted and expression measured for each using the NanoString platform, 79% of their 219 genes of interest showed significant correlation in expression between the 2 samples.3 Validation of the panel and discovery of the optimal algorithms and gene sets are eagerly awaited. In this edition of Transplantation, Smith et al4 assessed gene expression from 326 archival renal transplant FFPE biopsies using the NanoString B-HOT panel, with allograft diagnoses assigned according to the current Banff criteria.5 Pathologic diagnoses included T cell–mediated rejection, chronic antibody-mediated rejection, borderline/suspicious, normal histology, acute tubular injury, and others, although active antibody-mediated rejection was not represented. The expression of the 770 genes was analyzed by principal components using 3 different methods, with subsequent modeling to determine their ability to identify and distinguish various transplant diagnoses. The authors found that, compared with published diagnostic microarray gene sets, B-HOT transcript analysis of routine FFPE clinical biopsies yielded a similar correspondence to various pathologic diagnoses. Misclassification rates—that is, discrepancies with the pathologic diagnosis—varied for different phenotypes. The study follows recently published work from the same author who conducted in silico statistical analyses from archival public microarray data of human renal allograft biopsies, which showed that the B-HOT panel genes as a subset of microarray genes readily identify rejection and nonrejection diagnoses.6 As the author suggested, this is not surprising because the genes on the B-HOT panel are predominantly derived from prior validated microarray studies. Future studies comparing the B-HOT panel against established microarray gene sets should take this into consideration. As the current consensus gene set is nonproprietary, it has generated great interest because the evaluation of the genes can be undertaken on any molecular analytic platform and is not restricted to the use of the commercially available panel with NanoString. This study by Smith represents the very recent efforts by researchers to establish and validate predictive models/classification systems for differential rejection diagnosis using the gene set.7,8 So far, mixed rejection has proven to be a challenging histological classification, with mediocre performance characteristics using molecular diagnostics. The commercial B-HOT panel comprises 770 genes spanning multiple rejection, immune response, and tissue damage pathways, but the panel is customizable, allowing an additional 30 genes of the user’s choosing to be included. There is certainly room for further “optimization” to enhance diagnostic precision. Ultimately, there does not necessarily need to be a single “best” molecular test using a specific platform but tools to improve on the current clinical practice. Facilitating access to validated tools is key in promoting greater utilization and uptake of molecular diagnostics in transplantation. The strong interest in this area of transplant research is complemented by the expanding armamentarium of molecular platforms. Technological developments now permit the use of both FFPE and frozen tissue for single-cell/single-nucleus and spatial RNAseq experiments. These will allow for better cell-type identification, cell-cell interaction, and spatial evaluation of biopsy adequacy and injury to support biologic validation. These may help further inform and refine “consensus” gene sets. Optimization of the gene set, development and evaluation of analysis pipelines and classification models, and multicenter validation studies are anticipated in the years to come. Whether B-HOT lives up to its name remains to be seen. ACKNOWLEDGMENTS J.S.Y.L is a recipient of the National Health and Medical Research Council postgraduate scholarship (GNT116877) and the Westmead Association BJ Amos Travelling Scholarship.