Eight cases of disseminated neoplasia were found among 540 specimens of Mytilus edulis collected from an intertidal beach in Connecticut in western Long Island Sound. This was unusual, because disseminated neoplasia is very rare in M. edulis but causes epizootic mortalities in another mussel species, M. trossulus. According to histology, mussels showed a continuum of disease progression, from early stages with a few anaplastic cells around the stomach epithelium to more advanced cases with multiple foci of neoplastic cells in the tissues, finally to terminal cases with profuse infiltration of neoplastic cells in all tissues. Flowcytometric hemocyte analyses were performed to compare immune functions between neoplastic and healthy mussels. Circulating hemocytes from the neoplastic mussels showed significantly less phagocytosis and significantly more apoptosis than hemocytes from the healthy mussels. Hemocyte cell density measured by flow cytometry increased in the hemolymph with progression of the disease on histological sections. In situ hybridization was performed to detect apoptosis also on paraffin sections. There were more apoptotic neoplastic cells in the early stages of the disease than in the later stages. These observations suggest the need for further studies on apoptosis-regulating genes to explain differences in susceptibility to neoplasia of different Mytilus species, and the role of apoptosis in the progression of disseminated neoplasia.