Since 2014, blue mussel industry in France has been facing heavy mortality outbreaks (90–100%) affecting both juveniles and adults. This report presents evidence of heavy genomic abnormalities associated with mortality outbreaks in blue mussels from the Atlantic coast of France. Ploidy characteristics of hemic cells were investigated using Flow CytoMetry (FCM), revealing an unusual, broad continuum of ploidy distribution from hypodiploidy to tetraploidy. FCM was additionally used to evaluate, at individual and populations levels, different thresholds of genomic abnormality (GA%)using the percentage of non-diploid nuclei. Individual mussels were considered to be abnormal when more than 10% of hemocytes in S–G2/M phase were present. At the population level, a threshold of 6% for the mean intensity of the abnormality is proposed. GA% was found to be significantly predictive of the final mortality Based on the established thresholds, only two mussel stocks analyzed in this study were considered to have good cytogenetic quality, while all other stocks appeared to be affected. FCM offers a very powerful tool to help manage current blue mussel mortality in France. We also believe that annual and extensive determination of cytogenetic quality of wild and cultivated mussel beds along with exclusive use of FCM-qualified mussel seeds should be a priority.