Hemocytic Neoplasia (HN) is a transmissible cancerous disease-causing significant mortality in Mercenaria mercenaria (quahog) aquaculture in Massachusetts and has been identified in quahog stocks in other states including Rhode Island, New Jersey, and Florida. Previous studies have identified candidate genetic markers for detecting HN in quahogs; however, they were unspecific to HN and were only effective at identifying moderate to severe cases of the infection. In this study we aim to differentiate gene expression profiles between HN and non-HN cells to pinpoint cancer-specific genes as well as characterize key pathways and molecular functions associated with HN. Naive HN-negative quahogs were exposed in cohabitation with HN-positive clams for up to 90 days, and samples of hemocytes were collected at different times after exposure to represent early and late-stage infection. Pools of hemocytes from infected neoplastic and non-neoplastic control clams (as determined using hemocyte smears) were processed for single cell sequencing analysis using 10X Genomics Single Cell Multiome ATAC + GEX Gel Beads followed by 10X Genomics Chromium Single Cell Sequencing. Data analysis revealed 23 clusters of hemocytes based on their individual gene expression profile (Fig. 1). Differential gene expression analysis identified significantly upregulated genes that are only present in neoplastic clams and are signatures of cancer in humans (e.g. transforming growth factor-beta-induced protein ig-h3-like, glutathione S-transferase-like, cytochrome P450 2B19-like, probable G-protein coupled receptor CG31760, secreted frizzled-related protein 3-like, and synaptotagmin-4-like). Additionally, KEGG pathway enrichment analysis revealed that several pathways are significantly enriched only in HN-positive cells. These pathways include RNA degradation, ribosome biogenesis, and nucleotide excision repair, all of which are involved in genetic information processing. Further work is currently underway characterizing enriched pathways and regulated genes in quahogs at early stages of infection. This information will be used to develop accurate and fast molecular methods of HN diagnosis of the disease using an RT-qPCR method.