This study investigates the prevalence and characteristics of disseminated neoplasia (DN) in Mytilus chilensis in the Los Lagos Region of southern Chile. DN is a malignant proliferative disease that has been described in several species of the genus Mytilus. More than 4.000 adult mussels, both cultured and natural, collected between 2016 and 2022 in different geographical areas (Calbuco-Hueihue, Castro, Quello<acute accent>n) and seasons (winter-spring, summer-autumn) were histologically analysed. The prevalence was assessed and three levels of severity of DN were defined, based on number of neoplastic cells and organs invaded. Morphology and morphometry of neoplastic cells and hemocytes were evaluated. Cell and nucleus diameters and the nucleus/cytoplasm ratio of granulocytes and hyalinocytes were analysed in healthy and neoplastic individuals. The size of neoplastic cells was significantly larger in stage 3 of neoplasia than in stage 1. The overall mean prevalence of DN in M. chilensis was 3.4%, significant differences were found between sites, being higher in Calbuco-Hueihue (5.59%) than in Castro (3.78%) and Quello<acute accent>n (1.40%). The prevalence was significantly higher in the winter-spring season (7.79%) than in the summer-autumn season (3.95%) in Calbuco-Hueihue. The sex, gametogenic stage, and Adipogranular (ADG) cells status were recorded for each mussel, and related to the severity stages of DN. For stages 1 and 2 of DN, females and males could be recognized, but in stage 3 almost no evidence of sex remained. The same trend was identified for the gonadal status, the advanced stages of DN were associated with castration of the mussels. The ADG cells status was highest at stage 1 of DN, declining in number and staining till stage 3. The sex ratio of healthy mussels was 53.5% female, 43.7% male, 1.6% hermaphrodite, and 1.3% indeterminate, for mussels with DN it was 34.1% female, 16% male, 2.2% hermaphrodite and 47.8% indeterminate. Occurrence of DN was higher in females, but the severity stages affected equally female and male mussels. Although the overall prevalence is low, there are some potential risks that warrant continued monitoring and further study of disseminated neoplasia in M. chilensis. This study provides important data on the epidemiology of DN in M. chilensis, which will inform future research and management strategies in aquaculture.