Transmissible cancers are infectious parasitic clones of malignant cells that metastasize to new hosts, living past the death of the founder animal in which the cancer initiated. Several lineages of transmissible cancer have recently been identified in bivalves, including one that has spread through the soft-shell clam (Mya arenaria) population along the east coast of North America. To investigate the evolutionary history of this transmissible cancer lineage, we assembled a highly contiguous 1.2 Gb soft-shell clam reference genome and characterized somatic mutations from cancer sequences.